The aim of this study was to evaluate the role of the pulmonary vessel endothelium in the metabolism of fibrinogen (FBG), by measuring the FBG, D-dimer, and fibrin(ogen) degradation product levels in the blood from pulmonary and radial arteries from 99 patients undergoing aortocoronary bypass. For comparison, protein C, protein S, and factor VII, were also measured. The results showed, with respect to the pulmonary arterial blood levels, significantly lower FBG levels (3.72 +/- 0.83 vs 3.66 +/- 0.81 g/L; P < .001) and higher fibrin(ogen) degradation product levels (7.36 +/- 1.53 vs 8.15 +/- 1.59 mg/L; P < .000 01) in the radial arterial blood. No difference was found for d -dimer, protein C, protein S, and factor VII. The study demonstrated that the pulmonary capillary endothelium contributes to the FBG catabolism for about a 0.02 fractional rate and support the view of an endothelial FBG catabolic pathway as the main catabolic pathway, owing to the fact that the pulmonary endothelial surface is about a 0.1 fraction of the peripheral vessel endothelial surface. 相似文献
AIMS: C-reactive protein is associated with risk of cardiovascular disease. However, whether C-reactive protein is a marker of severity of cardiovascular disease or actually is involved in its pathogenesis remains unknown. We investigated the relation between C-reactive protein haplotypes, representing the comprehensive variation of the C-reactive protein gene, and coronary heart disease. METHODS AND RESULTS: The Rotterdam Study is a prospective population-based study among men and women aged 55 years and older. C-reactive protein was associated with risk of coronary heart disease, with a multivariable adjusted hazard ratio of 1.9 (95% CI 1.5-2.4) for the highest vs. the lowest quartile. Four C-reactive protein haplotypes were present with overall frequencies of 32.8, 31.7, 29.5, and 5.9%. C-reactive protein serum levels were significantly different according to C-reactive protein haplotypes. C-reactive protein haplotypes were not associated with coronary heart disease. CONCLUSION: Steady-state C-reactive protein serum level is influenced by C-reactive protein gene haplotypes. Although elevated C-reactive protein level has lately been found to be a consistent and relatively strong risk factor for cardiovascular disease, our study does not support that the common variation in the C-reactive protein gene has a large effect on the occurrence of coronary heart disease. 相似文献
Endothelial cell calcium flux is critical for leukocyte transendothelial migration (TEM), which in turn is essential for the inflammatory response. Intravital microscopy of endothelial cell calcium dynamics reveals that calcium increases locally and transiently around the transmigration pore during TEM. Endothelial calmodulin (CaM), a key calcium signaling protein, interacts with the IQ domain of IQGAP1, which is localized to endothelial junctions and is required for TEM. In the presence of calcium, CaM binds endothelial calcium/calmodulin kinase IIδ (CaMKIIδ). Disrupting the function of CaM or CaMKII with small-molecule inhibitors, expression of a CaMKII inhibitory peptide, or expression of dominant negative CaMKIIδ significantly reduces TEM by interfering with the delivery of the lateral border recycling compartment (LBRC) to the site of TEM. Endothelial CaMKII is also required for TEM in vivo as shown in two independent mouse models. These findings highlight novel roles for endothelial CaM and CaMKIIδ in transducing the spatiotemporally restricted calcium signaling required for TEM. 相似文献
Copper-zinc superoxide dismutase-1 (SOD1) is the second most common mutated gene in amyotrophic lateral sclerosis (ALS). To date more than 150 missense mutations of SOD1 have been reported. The objective of this study was to describe a novel SOD1 mutation and its phenotypic expression. We describe a 74-year-old Caucasian man who began to complain of progressive weakness and atrophy of the right hand and over 10 months developed a severe tetraparesis, with atrophies of upper and lower limbs and neck muscles, dysphagia, and dyspnea that led to percutaneous endoscopic gastrostomy and tracheotomy. A diagnosis of ALS was made. Genetic analysis identified a heterozygous mutation in exon 4 of SOD1 that results in the amino acid substitution from arginine to cysteine at position 115 (p.R115C). We identified a novel pathogenic SOD1 mutation in a patient with a very rapid disease progression and aggressive phenotype providing additional information on the wide range of SOD1 mutations in apparently sporadic ALS and confirming the possibility of a strong genotype-phenotype correlation for distinct SOD1 mutations. 相似文献
Previous cross-sectional studies suggested an association between attachment-related avoidance and altered immune function. We aimed at testing this hypothesis with longitudinal data. A random sample of 65 female nurses provided a blood sample and completed measures of perceived stress, social support, alexithymia, and attachment style. Immune assays included lymphocyte proliferative response (LPR) to Phytohemagglutinin and NK cell cytotoxicity (NKCC). State measures (perceived stress and support) and immune measures were collected again after 4, 8, and 12 months. Linear mixed effects models were used to examine the relationship between attachment and immunity. While low to moderate levels of attachment-related avoidance were not associated with NKCC, there was a significant negative association (beta −.35; p = .005) between high levels of avoidance and NKCC. No association was observed between NKCC and attachment-related anxiety, and between LPR and both attachment dimensions. While our findings should be interpreted with caution due to study limitations such as the relatively small sample size and the inclusion of only female participants, they corroborate the notion that attachment is linked to physiology and health. 相似文献
Sport Sciences for Health - The Pilates method has become a popular exercise modality. However, there is little information on the energy expenditure (EE) and aerobic metabolism involved in a... 相似文献
Journal of Neurology - Previous studies have reported an association between anti-tumor necrosis factor alpha (anti-TNFα) treatment and central nervous system (CNS) events. We described eight... 相似文献
SARS-CoV-2 infection leads to high viral loads in the upper respiratory tract that may be determinant in virus dissemination. The extent of intranasal antiviral response in relation to symptoms is unknown. Understanding how local innate responses control virus is key in the development of therapeutic approaches.
Methods
SARS-CoV-2-infected patients were enrolled in an observational study conducted at the Geneva University Hospitals, Switzerland, investigating virological and immunological characteristics. Nasal wash and serum specimens from a subset of patients were collected to measure viral load, IgA specific for the S1 domain of the spike protein, and a cytokine panel at different time points after infection; cytokine levels were analyzed in relation to symptoms.
Results
Samples from 13 SARS-CoV-2-infected patients and six controls were analyzed. We found an increase in CXCL10 and IL-6, whose levels remained elevated for up to 3 weeks after symptom onset. SARS-CoV-2 infection also induced CCL2 and GM-CSF, suggesting local recruitment and activation of myeloid cells. Local cytokine levels correlated with viral load but not with serum cytokine levels, nor with specific symptoms, including anosmia. Some patients had S1-specific IgA in the nasal cavity while almost none had IgG.
Conclusion
The nasal epithelium is an active site of cytokine response against SARS-CoV-2 that can last more than 2 weeks; in this mild COVID-19 cohort, anosmia was not associated with increases in any locally produced cytokines.