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Nitric oxide mediates suppression of T cell responses in murine Trypanosoma brucei infection

African trypanosomes induce a generalized state of immunosuppression in their mammalian hosts. One characteristic of this is a suppression of lymphocyte responses to mitogen, which is mediated by suppressor macrophages. We investigated the involvement of nitric oxide in this phenomenon. Both peritoneal and splenic cell cultures from infected mice released nitrite and this was inhibitable by NG-mon

Vitamin K1 intake is associated with higher bone mineral density and reduced bone resorption in early postmenopausal Scottish women : no evidence of gene-nutrient interaction with apolipoprotein E polymorphisms

BACKGROUND: Polymorphisms in the apolipoprotein E (APOE) gene are associated with fracture risk, and a potential mechanism is through vitamin K transport.OBJECTIVE: We investigated the relation between dietary vitamin K(1) intake, APOE polymorphisms, and markers of bone health.DESIGN: We measured bone mineral density (BMD) at the lumbar spine (LS) and femoral neck (FN) in a cohort of Scottish wome

Large-scale analysis of association between polymorphisms in the transforming growth factor beta 1 gene (TGFB1) and osteoporosis : the GENOMOS study

INTRODUCTION: The TGFB1 gene which encodes transforming growth factor beta 1, is a strong candidate for susceptibility to osteoporosis and several studies have reported associations between bone mineral density (BMD), osteoporotic fractures and polymorphisms of TGFB1, although these studies have yielded conflicting results.METHODS: We investigated associations between TGFB1 polymorphisms and BMD a

Large-scale population-based study shows no evidence of association between common polymorphism of the VDR gene and BMD in British women

UNLABELLED: The VDR is a candidate gene for osteoporosis. Here we studied five common polymorphisms of VDR in relation to calcium intake and vitamin D status in a population-based cohort of 3100 British women, but found no significant association with bone mass, bone loss, or fracture.INTRODUCTION: Population studies of vitamin D receptor (VDR) polymorphisms have produced conflicting results. We p

Polymorphisms of the CLCN7 gene are associated with BMD in women

UNLABELLED: Here we show that a common polymorphism causing a valine to methionine amino acid substitution at codon 418 (V418M) in the CLCN7 gene is associated with femoral neck BMD in women. Our study adds to accumulating evidence that shows that common allelic variants in monogenic bone disease genes often contribute to BMD regulation in normal subjects.INTRODUCTION: The CLCN7 gene is a strong c

Interspecies synteny mapping identifies a quantitative trait locus for bone mineral density on human chromosome Xp22

Bone mineral density (BMD) is a complex trait with a strong genetic component and an important predictor of osteoporotic fracture risk. Here we report the use of a cross-species strategy to identify genes that regulate BMD, proceeding from quantitative trait mapping in mice to association mapping of the syntenic region in the human genome. We identified a quantitative trait locus (QTL) on the mous

Methylenetetrahydrofolate reductase polymorphism interacts with riboflavin intake to influence bone mineral density

Bone mineral density is a complex trait regulated by an interaction between genetic and environmental factors. Recent studies have identified a functional polymorphism affecting codon 677 of the methylenetetrahydrofolate reductase (MTHFR) gene that is associated with reduced bone mineral density (BMD) in Japanese and Danish postmenopausal women and increased risk of fracture in elderly Danish wome

Susceptibility to Paget's disease of bone is influenced by a common polymorphic variant of osteoprotegerin

UNLABELLED: To clarify the role of the TNFRSF11B gene encoding osteoprotegerin (OPG), in Paget's disease of bone (PDB) we studied TNFRSF11B polymorphisms in an association study of 690 UK subjects and in a worldwide familial study of 66 kindreds. We found that the G1181 allele of TNFRSF11B, encoding lysine at codon 3 of the OPG protein, predisposes to both sporadic and familial PDB.INTRODUCTION: P

Association of the Pro12Ala and C1431T variants of PPARG and their haplotypes with susceptibility to Type 2 diabetes

AIMS/HYPOTHESIS: The Pro12Ala polymorphism of peroxisome proliferator-activated receptor (PPAR)gamma has been consistently associated with Type 2 diabetes. The rare Ala12 variant is estimated to reduce the risk of developing Type 2 diabetes by 20 percent. This variant is in linkage disequilibrium with another common variant, T1431. Both have opposing associations with body weight. We therefore exa

Association between a polymorphism affecting an AP1 binding site in the promoter of the TCIRG1 gene and bone mass in women

The TCIRG1 gene encodes a component of the osteoclast vacuolar proton pump and previous work has shown that inactivating mutations of the TCIRG1 cause autosomal recessive osteopetrosis. In order to determine whether allelic variation in TCIRG1 contributes to the regulation of bone mineral density (BMD) in normal individuals, we studied the relationship between polymorphisms of TCIRG1 and BMD in a

Effect of a COL1A1 Sp1 binding site polymorphism on arterial pulse wave velocity : an index of compliance

-Reduced arterial compliance precedes changes in blood pressure, which may be mediated through alterations in vessel wall matrix composition. We investigated the effect of the collagen type I-alpha1 gene (COL1A1) +2046G>T polymorphism on arterial compliance in healthy individuals. We recruited 489 subjects (251 men and 238 women; mean age, 22.6+/-1.6 years). COL1A1 genotypes were determined using

Susceptibility to osteoporotic fracture is determined by allelic variation at the Sp1 site, rather than other polymorphic sites at the COL1A1 locus

Previous studies have identified an association between osteoporotic fracture and a polymorphism affecting a Sp1 binding site in the first intron of the collagen type I alpha 1 gene (COL1A1). It is currently unclear, however, whether this association is direct or the result of linkage disequilibrium with other polymorphisms situated nearby. In this study we analyzed the relationship between four w

Relation of alleles of the collagen type Ialpha1 gene to bone density and the risk of osteoporotic fractures in postmenopausal women

BACKGROUND: Osteoporosis is a common disorder with a strong genetic component. One way in which the genetic component could be expressed is through polymorphism of COLIA1, the gene for collagen type Ialpha1, a bone-matrix protein.METHODS: We determined the COLIA1 genotypes SS, Ss, and ss in a population-based sample of 1778 postmenopausal women using a polymerase-chain-reaction-based assay. We the

Polymorphisms of the interleukin-6 gene are associated with bone mineral density

Genetic factors play an important role in determining bone mass and several genes probably act as regulators of this process. Interleukin-6 (IL-6) is a candidate gene for regulation of bone density, since it has stimulatory effects on cells of the osteoclast lineage and has been implicated in the pathogenesis of bone loss associated with estrogen deficiency. Here we studied the relationship betwee

Single nucleotide polymorphism detection : allelic discrimination using TaqMan

Candidate gene studies are one of the most widely used approaches in the dissection of the genetic basis of disease. High-throughput methods for genotyping single nucleotide polymorphisms (SNPs) are necessary to perform large-scale association studies. We describe the use of the TaqMan or 5' nuclease allelic discrimination assay for genotyping polymorphisms of the collagen I alpha 1 (COLIA1) and v

From passive passenger to participating co-pilot – Pregnant women's expectations of being able to access their online journal from antenatal care

Objective The aim of the study was to describe pregnant women's expectations of being able to access their electronic health records from antenatal care. Methods Nine pregnant women passing 25 full gestational weeks were interviewed individually. Collected data were analysed with an inductive approach using content analysis. The study was performed in antenatal care units in southern Sweden. Resul

Liver diseases in Adult Life after Childhood Cancer in Scandinavia (ALiCCS) : A population-based cohort study of 32,839 one-year survivors

Information on late onset liver complications after childhood cancer is scarce. To ensure an appropriate follow-up of childhood cancer survivors and reducing late liver complications, the need for comprehensive and accurate information is presented. We evaluate the risk of liver diseases in a large childhood cancer survivor cohort. We included all 1-year survivors of childhood cancer treated in th

Association between vitamin D receptor gene polymorphisms, falls, balance and muscle power : results from two independent studies (APOSS and OPUS)

SUMMARY: Fall prevention is a key strategy for reducing osteoporotic fractures. We investigated the association between vitamin D receptor (VDR) polymorphisms and reported falls in postmenopausal women. Bsm1 polymorphisms were associated with falls, balance and muscle power measurements. These results may explain some of the excess fracture risk associated with VDR in some studies.INTRODUCTION: Fa

Current evidence of oral anticoagulant reversal : A systematic review

Introduction Approximately 4–6% of patients treated with oral anticoagulants (OAC) will suffer from major hemorrhage or be in need of urgent surgery necessitating anticoagulant reversal therapy. Several new oral anticoagulants and reversal agents have been introduced that make it difficult for physicians to stay updated on the current evidence of reversal management. This study aims to review the

Total Synthesis of Dehaloperophoramidine : Evolution of a Synthesis

This account describes our efforts toward developing a stereodivergent entry to perophoramidine and the communesin alkaloids. The original approach toward our simplified model substrates relied on a palladium-catalyzed carbopalladation–carbonylation of a tetrasubstituted olefin to install the vicinal all-carbon quaternary stereocenters present in the target molecules, the olefin's stereochemistry