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Immunization with advanced glycation end products modified low density lipoprotein inhibits atherosclerosis progression in diabetic apoE and LDLR null mice

Background: Diabetes accelerates atherosclerosis through undefined molecular mechanisms. Hyperglycemia induces formation of advanced glycation end product (AGE)-modified low-density lipoprotein (LDL). Anti-AGE-LDL autoantibodies favor atherosclerosis (AS) progression in humans, while anti oxidized LDL immunization inhibits AS in hypercholesterolemic, non-diabetic mice. We here investigated if AGE-

The pro-inflammatory effect of uraemia overrules the anti-atherogenic potential of immunization with oxidized LDL in apoE-/- mice

Background. Uraemia increases oxidative stress, plasma titres of antibodies recognizing oxidized low-density lipoprotein (oxLDL) and development of atherosclerosis. Immunization with oxLDL prevents classical, non-uraemic atherosclerosis. We have investigated whether immunization with oxLDL might also prevent uraemia-induced atherosclerosis in apolipoprotein E knockout (apoE-/-) mice. Methods. ApoE

Family history of venous thromboembolism as a risk factor and genetic research tool.

Familial clustering of venous thromboembolism (VTE) was described as far back as 1905 by Briggs. Although Egeberg discovered inherited deficiency of antithrombin in 1965, it was not until Dahlbäck discovered resistance to activated protein C in 1993 that it became clear that genetic factors are common risk factors of VTE. Several genes have been linked to familial aggregation of VTE and genome-wid

Biocompatibility of mannan nanogel-safe interaction with plasma proteins

Background: Self-assembled mannan nanogels are designed to provide a therapeutic or vaccine delivery platform based on the bioactive properties of mannan to target mannose receptor expressed on the surface of antigen-presenting cells, combined with the performance of nanogels as carriers of biologically active agents. Methods: Proteins in the corona around mannan nanogel formed in human plasma wer

Age at Menopause, Reproductive Life Span, and Type 2 Diabetes Risk

OBJECTIVE-Age at menopause is an important determinant of future health outcomes, but little is known about its relationship with type 2 diabetes. We examined the associations of menopausal age and reproductive life span (menopausal age minus menarcheal age) with diabetes risk. RESEARCH DESIGN AND METHODS-Data were obtained from the InterAct study, a prospective case-cohort study nested within the

Necrotizing myositis and septic shock caused by Haemophilus influenzae type f in a previously healthy man diagnosed with an IgG3 and a mannose-binding lectin deficiency

An increased incidence of infections by Haemophilus influenzae type f (Hif) has recently been suggested, but such infections have mainly been regarded as opportunistic. We present here a dramatic case of Hif necrotizing myositis and septic shock. A subsequently diagnosed IgG3 and mannose-binding lectin deficiency possibly contributed to the severe outcome.

Immunization with cationized BSA inhibits progression of disease in ApoBec-1/LDL receptor deficient mice with manifest atherosclerosis.

Immune responses against modified self-antigens generated by hypercholesterolemia play an important role in atherosclerosis identifying the immune system as a possible novel target for prevention and treatment of cardiovascular disease. It has recently been shown that these immune responses can be modulated by subcutaneous injection of adjuvant. In the present study we immunized 25-week old ApoBec

The Tetraspanin CD9 Affords High-Purity Capture of All Murine Hematopoietic Stem Cells

Prospective isolation is critical for understanding the cellular and molecular aspects of stem cell heterogeneity. Here, we identify the cell surface antigen CD9 as a positive marker that provides a simple alternative for hematopoietic stem cell isolation at high purity. Crucially, CD9 affords the capture of all hematopoietic stem cells in murine bone marrow in the absence of contaminating populat

Genetic variation in GIPR influences the glucose and insulin responses to an oral glucose challenge

Glucose levels 2 h after an oral glucose challenge are a clinical measure of glucose tolerance used in the diagnosis of type 2 diabetes. We report a meta-analysis of nine genome-wide association studies (n = 15,234 nondiabetic individuals) and a follow-up of 29 independent loci (n = 6,958-30,620). We identify variants at the GIPR locus associated with 2- h glucose level (rs10423928, beta (s.e.m.)

No Interactions Between Previously Associated 2-Hour Glucose Gene Variants and Physical Activity or BMI on 2-Hour Glucose Levels

Gene-lifestyle interactions have been suggested to contribute to the development of type 2 diabetes. Glucose levels 2 h after a standard 75-g glucose challenge are used to diagnose diabetes and are associated with both genetic and lifestyle factors. However, whether these factors interact to determine 2-h glucose levels is unknown. We meta-analyzed single nucleotide polymorphism (SNP) X BMI and SN

Expression of the RNA-binding protein RBM3 is associated with a favourable prognosis and cisplatin sensitivity in epithelial ovarian cancer

Background: We recently demonstrated that increased expression of the RNA-binding protein RBM3 is associated with a favourable prognosis in breast cancer. The aim of this study was to examine the prognostic value of RBM3 mRNA and protein expression in epithelial ovarian cancer (EOC) and the cisplatin response upon RBM3 depletion in a cisplatin-sensitive ovarian cancer cell line. Methods: RBM3 mRNA

Increased incidence of invasive bacterial disease in chronic obstructive pulmonary disease compared to the general population-a population based cohort study

Background: Innate defence mechanisms of the airways are impaired in chronic obstructive pulmonary disease (COPD), predisposing patients to lower respiratory tract infections, but less is known about the association with other infections. In this population-based cohort study, we investigated the associations between COPD and invasive bacterial disease by comparing incidence rates of bacteraemia i

Is nephrolithiasis an unrecognized extra-articular manifestation in ankylosing spondylitis? A prospective population-based Swedish national cohort study with matched general population comparator subjects.

Ankylosing spondylitis (AS) is associated with several extra-articular manifestations. Nephrolithiasis (NL) has not been recognized as one of those, however, several factors known to increase the risk of NL are at play in AS patients. The objective was to estimate rates and predictors of NL in Swedish patients with AS compared to the general population.

Potent Intratype Neutralizing Activity Distinguishes Human Immunodeficiency Virus Type 2 (HIV-2) from HIV-1

HIV-2 has a lower pathogenicity and transmission rate than HIV-1. Neutralizing antibodies could be contributing to these observations. Here we explored side by side potency and breadth of intratype and intertype neutralizing activity (NAc) in plasma of 20 HIV-1, 20 HIV-2 and 11 dually HIV-1/2 (HIV-D) seropositive individuals from Guinea-Bissau, West Africa. Panels of primary isolates, five HIV-1 a

Modeling the Time Evolution of the Nanoparticle-Protein Corona in a Body Fluid

Background: Nanoparticles in contact with biological fluids interact with proteins and other biomolecules, thus forming a dynamic corona whose composition varies over time due to continuous protein association and dissociation events. Eventually equilibrium is reached, at which point the continued exchange will not affect the composition of the corona. Results: We developed a simple and effective

Twelve type 2 diabetes susceptibility loci identified through large-scale association analysis

By combining genome-wide association data from 8,130 individuals with type 2 diabetes (T2D) and 38,987 controls of European descent and following up previously unidentified meta-analysis signals in a further 34,412 cases and 59,925 controls, we identified 12 new T2D association signals with combined P < 5 x 10(-8). These include a second independent signal at the KCNQ1 locus; the first report, to