Quantitative high-performance liquid chromatography-tandem mass spectrometry method for the analysis of free desmosines in plasma and urine.

A rapid method for the determination of the sum of free desmosine and isodesmosine in human plasma and urine is described. Efficient sample clean-up prior to LC-MS/MS analysis is mandatory for detection of free desmosines in plasma samples. The combination of ultra-filtration and a two-step solid phase extraction minimizes the sample complexity and ion suppression effects.

Phase II study of a neutrophil elastase inhibitor (AZD9668) in patients with bronchiectasis.

Unlabelled: Neutrophil elastase (NE) activity is increased in bronchiectasis and may play a role in this condition. We wished to determine the effect of AZD9668, a selective oral inhibitor of NE. Efficacy and safety of AZD9668 60 mg twice daily over 4 weeks were evaluated in a randomised, double-blind, placebo-controlled, parallel-group, Phase II, signal-searching study in patients with bronchiectasis.

Blood biomarkers and measures of pulmonary function--a study from the Swedish twin registry.

Objective: There is great need of biomarkers for research and clinical purposes in COPD. This study explored the relationships between ten putative plasma biomarkers of COPD and physiological measures of reduced lung function.

Methods: FEV(1), FVC, residual volume/total lung capacity (RV/TLC) and CO diffusion capacity (D(L)CO) were assessed in 357 subjects from the Swedish Twin Registry.

Efficacy, safety and effect on biomarkers of AZD9668 in cystic fibrosis.

The aim of this study was to evaluate the safety and effect on clinical outcomes and biomarkers of inflammation and tissue damage of the neutrophil elastase inhibitor AZD9668 (60 mg twice daily orally for 4 weeks) in cystic fibrosis. This was a randomised, double-blind, placebo-controlled study. Primary outcome measures were sputum neutrophil count, lung function, 24-h sputum weight, BronkoTest® diary card data and health-related quality-of-life (revised cystic fibrosis quality-of-life questionnaire).

Twins studies as a model for studies on the interaction between smoking and genetic factors in the development of chronic bronchitis.

Smoking is the main risk factor for COPD (chronic obstructive pulmonary disease) but genetic factors are of importance, since only a subset of smokers develops the disease. Sex differences have been suggested both in disease prevalence and response to environmental exposures. Furthermore, it has been shown that acquisition of 'addiction' to smoking is partly genetically mediated.

Positional identification of TNFSF4, encoding OX40 ligand, as a gene that influences atherosclerosis susceptibility.

Ath1 is a quantitative trait locus on mouse chromosome 1 that renders C57BL/6 mice susceptible and C3H/He mice resistant to diet-induced atherosclerosis. The quantitative trait locus region encompasses 11 known genes, including Tnfsf4 (also called Ox40l or Cd134l), which encodes OX40 ligand. Here we report that mice with targeted mutations of Tnfsf4 had significantly (P View Article and Find Full Text PDF

Locating Ath8, a locus for murine atherosclerosis susceptibility and testing several of its candidate genes in mice and humans.

A previous study revealed that the difference in susceptibility to atherosclerotic lesions between inbred mouse strains SM/J and NZB/BlNJ was determined by one major locus (Ath8). In this study a (SM/J x NZB/BlNJ) F(1) x SM/J backcross localized Ath8 by quantitative trait locus mapping to chromosome 4 with a suggestive LOD score of 2.7.

Peroxiredoxin 6 deficiency and atherosclerosis susceptibility in mice: significance of genetic background for assessing atherosclerosis.

Peroxiredoxin 6 (Prdx6; also called antioxidant protein 2, or Aop2) is a candidate gene for Ath1, a locus responsible for the respective susceptibility and resistance of mouse strains C57BL/6J (B6) and C3H/HeJ (C3H) to diet-induced atherosclerosis. To evaluate if Prdx6 underlies Ath1, we compared the diet-induced atherosclerotic lesions in Prdx6 targeted mutant (Prdx6-/-) mice of different genetic backgrounds: B6, 129, and B6;129. PRDX6 protein and mRNA were expressed in normal and atherosclerotic aortas.

Quantitative trait loci that determine plasma lipids and obesity in C57BL/6J and 129S1/SvImJ inbred mice.

The plasma lipid concentrations and obesity of C57BL/6J (B6) and 129S1/SvImJ (129) inbred mouse strains fed a high-fat diet containing 15% dairy fat, 1% cholesterol, and 0.5% cholic acid differ markedly. To identify the loci controlling these traits, we conducted a quantitative trait loci (QTL) analysis of 294 (B6 x 129) F(2) females fed a high-fat diet for 14 weeks.

Quantitative trait loci analysis for plasma HDL-cholesterol concentrations and atherosclerosis susceptibility between inbred mouse strains C57BL/6J and 129S1/SvImJ.

Objective: The C57BL/6 (B6) and 129 mouse inbred strains differ markedly in plasma HDL-cholesterol concentrations and atherosclerosis susceptibility after a high-fat diet consumption. To identify loci controlling these traits, we performed quantitative trait loci (QTL) analysis.

Methods And Results: We fed a high-fat diet to 294 (B6x129S1/SvImJ)F2 females for 14 weeks, measured plasma HDL concentrations and size of aortic fatty-streak lesions, genotyped F2 females, and performed QTL analysis.

Mice with targeted mutation of peroxiredoxin 6 develop normally but are susceptible to oxidative stress.

Reactive oxygen species, especially hydrogen peroxide, are important in cellular signal transduction. However, excessive amounts of these species damage tissues and cells by oxidizing virtually all important biomolecules. Peroxiredoxin 6 (PRDX6) (also called antioxidant protein 2, or AOP2) is a novel peroxiredoxin family member whose function in vivo is unknown.

A nonsense mutation in the enamelin gene causes local hypoplastic autosomal dominant amelogenesis imperfecta (AIH2).

Amelogenesis imperfecta (AI) is an inherited tooth disorder affecting tooth enamel formation only. A gene for autosomal dominant AI, the local hypoplastic form, has been localized to a 4 Mb region on chromosome 4q (AIH2). The enamelin gene (ENAM ), has been mapped to chromosome 4q21, to the same region as AIH2, and was recently shown to be mutated in patients with smooth and thin hypoplastic autosomal dominant AI (ADAI).