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Low production of reactive oxygen species in granulocytes is associated with organ damage in systemic lupus erythematosus

Introduction: Polymorphonuclear leukocytes (PMN) are main effector cells in the acute immune response. While the specific role of PMN in systemic lupus erythematosus (SLE) and autoimmunity is still unclear, their importance in chronic inflammation is gaining more attention. Here we investigate aspects of function, bone marrow release and activation of PMN in patients with SLE. Methods: The followi

Low levels of IgG autoantibodies against the apolipoprotein B antigen p210 increases the risk of cardiovascular death after carotid endarterectomy.

Autoimmune responses against oxidized-LDL (oxLDL) have been suggested to modulate inflammation in atherosclerosis. Previous studies showed an association between autoantibodies against the apolipoprotein B (apoB) p210 antigen and a lower risk of cardiovascular (CV) events. In the present study we investigated if autoantibodies against p210 at the time of carotid endarterectomy (CEA) predict risk f

A1M/α1-Microglobulin Protects from Heme-Induced Placental and Renal Damage in a Pregnant Sheep Model of Preeclampsia.

Preeclampsia (PE) is a serious pregnancy complication that manifests as hypertension and proteinuria after the 20(th) gestation week. Previously, fetal hemoglobin (HbF) has been identified as a plausible causative factor. Cell-free Hb and its degradation products are known to cause oxidative stress and tissue damage, typical of the PE placenta. A1M (α1-microglobulin) is an endogenous scavenger of

Prospective study of merkel cell polyomavirus and risk of merkel cell carcinoma.

Merkel cell carcinoma (MCC) is a rare type of skin cancer that has a characteristically increased incidence among immunosuppressed subjects. The DNA of Merkel cell polyomavirus (MCV) is regularly found in most MCC tumors. We investigated whether Merkel cell polyomavirus (MCV) infection increases the risk for future Merkel cell carcinoma (MCC). Two large biobank cohorts (Southern Sweden Microbiolog

Ebf1 heterozygosity results in increased DNA damage in pro-B cells and their synergistic transformation by Pax5 haploinsufficiency.

Ebf1 is a transcription factor with documented dose dependent functions in normal and malignant B-lymphocyte development. To understand more about the roles of Ebf1 in malignant transformation, we investigated the impact of reduced functional Ebf1 dosage on mouse B-cell progenitors. Gene expression analysis suggested that Ebf1 was involved in the regulation of genes important for DNA repair as wel

Exosomes reflect the hypoxic status of glioma cells and mediate hypoxia-dependent activation of vascular cells during tumor development.

Hypoxia, or low oxygen tension, is a major regulator of tumor development and aggressiveness. However, how cancer cells adapt to hypoxia and communicate with their surrounding microenvironment during tumor development remain important questions. Here, we show that secreted vesicles with exosome characteristics mediate hypoxia-dependent intercellular signaling of the highly malignant brain tumor gl

Prediction of Significant Prostate Cancer Diagnosed 20 to 30 Years Later With a Single Measure of Prostate-Specific Antigen at or Before Age 50

BACKGROUND: We previously reported that a single prostate-specific antigen (PSA) measured at ages 44-50 was highly predictive of subsequent prostate cancer diagnosis in an unscreened population. Here we report an additional 7 years of follow-up. This provides replication using an independent data set and allows estimates of the association between early PSA and subsequent advanced cancer (clinical

Treatment with beta-blockers is associated with lower levels of Lp-PLA2 and suPAR in carotid plaques.

OBJECTIVES: To determine whether a long-term treatment with beta-blockers influences the inflammatory activity in carotid artery disease by reducing the carotid plaque levels of lipoprotein-associated phospholipase A2 (Lp-PLA2), its enzymatic products lysophosphatidylcholine (lysoPCs), and of soluble urokinase plasminogen activator receptor (suPAR). MATERIALS AND METHODS: One hundred and thirty-fo

Strategy for detection of prostate cancer based on relation between prostate specific antigen at age 40-55 and long term risk of metastasis: case-control study

Objective To determine the association between concentration of prostate specific antigen (PSA) at age 40-55 and subsequent risk of prostate cancer metastasis and mortality in an unscreened population to evaluate when to start screening for prostate cancer and whether rescreening could be risk stratified. Design Case-control study with 1: 3 matching nested within a highly representative population

Metastasis stimulation by hypoxia and acidosis-induced extracellular lipid uptake is mediated by proteoglycan-dependent endocytosis

Hypoxia and acidosis are inherent stress factors of the tumor microenvironment and have been linked to increased tumor aggressiveness and treatment resistance. Molecules involved in the adaptive mechanisms that drive stress-induced disease progression constitute interesting candidates of therapeutic intervention. Here, we provide evidence of a novel role of heparan sulfate proteoglycans (HSPG) in

Impaired phagocytosis and reactive oxygen species production in phagocytes is associated with systemic vasculitis

BACKGROUND: Anti-neutrophil cytoplasmic antibodies associated vasculitides (AAV) is a group of autoimmune diseases, characterized by small vessel inflammation. Phagocytes such as neutrophils and monocytes are the main effector cells found around the inflamed vessel wall. Therefore, we wanted to investigate aspects of function and activation of these cells in patients with AAV.METHODS: Flow cytomet

Small molecules increase direct neural conversion of human fibroblasts

The generation of human induced neurons (hiNs) via exogenous delivery of neural transcription factors represents a novel technique to obtain disease and patient specific neurons. These cells have the potential to be used for disease modeling, diagnostics and drug screening, and also to be further developed for brain repair. In the present study, we utilized hiNs to develop an unbiased screening as

Fast-track access to urologic care for patients with macroscopic haematuria is efficient and cost-effective : results from a prospective intervention study

Background:The delay between onset of macroscopic haematuria and diagnosis of bladder cancer is often long.Methods:We evaluated timely diagnosis and health-care costs for patients with macroscopic haematuria given fast-track access to diagnostics. During a 15-month period, a telephone hotline for fast-track diagnostics was provided in nine Swedish municipalities for patients aged ⩾50 years with ma

Germline CDKN2A Mutation Status and Survival in Familial Melanoma Cases

BACKGROUND: Germline mutations in CDKN2A have been associated with increased risk of melanoma and tobacco-related cancers in respiratory and upper digestive tissues. In CDKN2A wild-type (wt) melanoma families, other known high-risk, melanoma-predisposing mutations are rare, and no increased risk has been observed for nonskin cancers in this group. This study is the first to compare survival in ger

Postmenopausal hormone therapy and risk of stroke : A pooled analysis of data from population-based cohort studies

Background: Recent research indicates a favourable influence of postmenopausal hormone therapy (HT) if initiated early, but not late, on subclinical atherosclerosis. However, the clinical relevance of timing of HT initiation for hard end points such as stroke remains to be determined. Further, no previous research has considered the timing of initiation of HT in relation to haemorrhagic stroke ris

A low-spin Fe(iii) complex with 100-ps ligand-to-metal charge transfer photoluminescence

Transition-metal complexes are used as photosensitizers1, in light-emitting diodes, for biosensing and in photocatalysis2. A key feature in these applications is excitation from the ground state to a charge-transfer state3,4; the long charge-transfer-state lifetimes typical for complexes of ruthenium5 and other precious metals are often essential to ensure high performance. There is much interest

Genome-wide Scan Identifies Role for AOX1 in Prostate Cancer Survival

We performed genome-wide association studies and found single nucleotide polymorphisms (SNPs) at seven independent loci associated with prostate-cancer-specific survival time. Two SNPs replicated in an independent cohort. The SNP rs73055188 at AOX1 is associated with AOX1 gene expression level, which is correlated with biochemical recurrence.