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Low Levels of Circulating CD4+FoxP3+ T Cells Are Associated With an Increased Risk for Development of Myocardial Infarction But Not for Stroke.

OBJECTIVE: Regulatory T cells (Tregs) protect against atherosclerosis in experimental models, but their association with cardiovascular disease in humans remains to be elucidated. The aim of the present study was to determine whether circulating Tregs predict the development of acute cardiovascular events in humans. METHODS AND RESULTS: The study cohort consisted of a random sample of particip

Variability in the CIITA gene interacts with HLA in multiple sclerosis.

The human leukocyte antigen (HLA) is the main genetic determinant of multiple sclerosis (MS) risk. Within the HLA, the class II HLA-DRB1*15:01 allele exerts a disease-promoting effect, whereas the class I HLA-A*02 allele is protective. The CIITA gene is crucial for expression of class II HLA molecules and has previously been found to associate with several autoimmune diseases, including MS and typ

Glucose tolerance and beta-cell function in islet autoantibody-positive children recruited to a secondary prevention study.

AIMS: Children with type 1 diabetes (T1D) risk and islet autoantibodies are recruited to a secondary prevention study. The aims were to determine metabolic control in relation to human leukocyte antigen (HLA) genetic risk and islet autoantibodies in prepubertal children. METHODS: In 47 healthy children with GADA and at least one additional islet autoantibody, intravenous glucose tolerance test (Iv

Increased incidence of childhood, prostate and breast cancers in relatives of childhood cancer patients.

Whether cancer predisposing familial factors are associated with childhood tumors is unclear. The purpose was to study the incidence of childhood and adult tumors in extended families of children with cancer. Family history of cancer was obtained through questionnaires, and the Swedish Population-, and Cancer Registries for 194 childhood cancer patients aged ≤18 years, diagnosed 1972-2009. Standar

Prediction of Blood Pressure Changes Over Time and Incidence of Hypertension by a Genetic Risk Score in Swedes.

Recent Genome-Wide Association Studies (GWAS) have pinpointed different single nucleotide polymorphisms consistently associated with blood pressure (BP) and hypertension prevalence. However, little data exist regarding single nucleotide polymorphisms predicting BP variation over time and hypertension incidence. The aim of this study was to confirm the association of a genetic risk score (GRS), bas

Analytical Validation of the Automated Bone Scan Index as an Imaging Biomarker to Standardize the Quantitative Changes in Bone Scans of Patients with Metastatic Prostate Cancer.

A reproducible and quantitative imaging biomarker to standardize the evaluation of changes in bone scans is an unmet need for prostate cancer patients with skeletal metastasis. Here we have performed a series of analytical validation studies to evaluate the performance of the automated Bone Scan Index (BSI) as an imaging biomarker in patients with metastatic prostate cancer (mPCa).

Isolation of human induced pluripotent stem cell-derived dopaminergic progenitors by cell sorting for successful transplantation.

Human induced pluripotent stem cells (iPSCs) can provide a promising source of midbrain dopaminergic (DA) neurons for cell replacement therapy for Parkinson's disease. However, iPSC-derived donor cells inevitably contain tumorigenic or inappropriate cells. Here, we show that human iPSC-derived DA progenitor cells can be efficiently isolated by cell sorting using a floor plate marker, CORIN. We ind

Epithelial and Stromal MicroRNA Signatures of Columnar Cell Hyperplasia Linking Let-7c to Precancerous and Cancerous Breast Cancer Cell Proliferation.

Columnar cell hyperplasia (CCH) is the earliest histologically identifiable breast lesion linked to cancer progression and is characterized by increased proliferation, decreased apoptosis and elevated oestrogen receptor α (ERα) expression. The mechanisms underlying the initiation of these lesions have not been clarified but might involve early and fundamental changes in cancer progression. MiRNAs

Evaluation of the prognostic significance of MSMB and CRISP3 in prostate cancer using automated image analysis.

Despite prostate cancer being the most frequent cancer in men in the Western world, tissue biomarkers for predicting disease recurrence after surgery have not been incorporated into clinical practice. Our group has previously identified β-microseminoprotein (MSMB) and cysteine-rich secretory protein-3 (CRISP3) as independent predictors of biochemical recurrence after radical prostatectomy. The pur

Increased plasma level of soluble urokinase plasminogen activator receptor is associated with incidence of heart failure but not atrial fibrillation.

Soluble urokinase plasminogen activator receptor (suPAR) in plasma is a novel inflammatory marker thought to be released from the cell surface of neutrophils, T cells, and macrophages. Other inflammatory markers, mainly acute phase proteins produced in the liver, have been associated with the incidence of heart failure (HF) and atrial fibrillation (AF). We investigated the association between suPA

Fibromodulin Deficiency Reduces Low-Density Lipoprotein Accumulation in Atherosclerotic Plaques in Apolipoprotein E-Null Mice.

OBJECTIVE: The aim of this study was to analyze how an altered collagen structure affects development of atherosclerotic plaques. METHODS AND RESULTS: Fibromodulin-null mice develop an abnormal collagen fibril structure. In apolipoprotein E (ApoE)-null and ApoE/fibromodulin-null mice, a shear stress-modifying carotid artery cast induced formation of atherosclerotic plaques of different phenotypes;

Soluble urokinase plasminogen activator receptor in plasma is associated with incidence of CVD. Results from the Malmö Diet and Cancer Study.

BACKGROUND: Soluble urokinase plasminogen activator receptor (suPAR) is a highly sensitive marker that reflects increased inflammation and is positively correlated with pro-inflammatory biomarkers. The aim of this study was to explore the relationship between suPAR, cardiovascular disease (CVD) risk factors and incidence of CVD. METHODS: suPAR was assessed in a random sample of participants (N=569

Low expression of SHP-2 is associated with less favorable prostate cancer outcomes.

ABSTACT: Src homology 2 domain-containing tyrosine phosphatase-2 (SHP-2) is an important regulator of cell signaling because of its ability to dephosphorylate receptors of growth factors as well as the cytokines and tyrosine-phosphorylated proteins associated with these receptors. In the current study, we used four different prostate cancer cell lines: PC3, DU145, LNCaP and LNCaP-IL6+. Tumor speci

Adrenomedullin is a marker of carotid plaques and intima-media thickness as well as brachial pulse pressure.

Adrenomodulin (ADM) is a peptide hormone secreted in response to cellular strain such as ischemia and is believed to have a beneficial effect on the cardiovascular system. However, the epidemiological relationships between ADM and measurements of haemodynamics, arteriosclerosis and atherosclerosis are not well established. The aim of this study was to investigate the association between the mid-re

Ceruloplasmin and atrial fibrillation: evidence of causality from a population-based Mendelian randomization study.

Inflammatory diseases and inflammatory markers secreted by the liver, including C-reactive protein (CRP) and ceruloplasmin, have been associated with incident atrial fibrillation (AF). Genetic studies have not supported a causal relationship between CRP and AF, but the relationship between ceruloplasmin and AF has not been studied. The purpose of this Mendelian randomization study was to explore w

Inhibition of HIV-1 disease progression by contemporaneous HIV-2 infection.

BACKGROUND: Progressive immune dysfunction and the acquired immunodeficiency syndrome (AIDS) develop in most persons with untreated infection with human immunodeficiency virus type 1 (HIV-1) but in only approximately 20 to 30% of persons infected with HIV type 2 (HIV-2); among persons infected with both types, the natural history of disease progression is poorly understood. METHODS: We analyzed d

Altered profile of basket cell afferent synapses in hyper-excitable dentate gyrus revealed by optogenetic and two-pathway stimulations.

Cholecystokinin (CCK-) positive basket cells form a distinct class of inhibitory GABAergic interneurons, proposed to act as fine-tuning devices of hippocampal gamma-frequency (30-90 Hz) oscillations, which can convert into higher frequency seizure activity. Therefore, CCK-basket cells may play an important role in regulation of hyper-excitability and seizures in the hippocampus. In normal conditio

Genetic fine mapping and genomic annotation defines causal mechanisms at type 2 diabetes susceptibility loci.

We performed fine mapping of 39 established type 2 diabetes (T2D) loci in 27,206 cases and 57,574 controls of European ancestry. We identified 49 distinct association signals at these loci, including five mapping in or near KCNQ1. 'Credible sets' of the variants most likely to drive each distinct signal mapped predominantly to noncoding sequence, implying that association with T2D is mediated thro

Efficient expansion and dopaminergic differentiation of human fetal ventral midbrain neural stem cells by midbrain morphogens

Human fetal midbrain tissue grafting has provided proof-of-concept for dopamine cell replacement therapy (CRT) in Parkinson's disease (PD). However, limited tissue availability has hindered the development and widespread use of this experimental therapy. Here we present a method for generating large numbers of midbrain dopaminergic (DA) neurons based on expanding and differentiating neural stem/pr

Feasibility Study on Measuring Selected Proteins in Malignant Melanoma Tissue by SRM Quantification.

Currently there are no clinically recognized molecular biomarkers for malignant melanoma (MM) for either diagnosing disease stage or measuring response to therapy. The aim of this feasibility study was to develop targeted selected reaction monitoring (SRM) assays for identifying candidate protein biomarkers in metastatic melanoma tissue lysate. In a pilot study applying the SRM assay, the tissue e