Endothelium-dependent vascular responses induced by leukotriene B4

Leukotriene B(4) (LTB(4)) is an inflammatory mediator derived from the 5-lipoxygenase pathway of arachidonic acid metabolism and has recently implicated in the pathogenesis of atherosclerosis. There are two membrane bound receptors for LTB(4): BLT(1) and BLT(2), which represent the high and low affinity receptors, respectively. BLT receptors are expressed on leukocytes, and LTB(4) is a potent chemoattractant for neutrophils, eosinophils, and T lymphocytes. Recent studies have in addition shown that LTB(4) is an indirectly acting vasoconstrictor of isolated vascular preparations. In the guinea pig aorta, the LTB(4)-induced contractions were inhibited by endothelium-denudation. In addition, pre-treatment with the NO synthase inhibitor, L-NOARG, significantly enhanced the contractions induced by LTB(4). The contractile response induced by LTB(4) in the guinea pig aorta was abolished by the selective BLT(1) receptor antagonist U75302 and the expression of BLT(1) receptor mRNA in the guinea pig aorta was established by RT-PCR. Taken together, these results suggest that LTB(4) activates BLT(1) receptors on the endothelium of the guinea pig aorta, associated with the release of both contractile factors and NO.     

Helicobacter pylori infection and gastroesophageal reflux in a population-based study (The HUNT Study)

BACKGROUND AND AIM: It has been suggested that Helicobacter pylori infection may prevent gastroesophageal reflux, possibly through gastric atrophy. Since, however, previous results are contradictory and no population-based studies are available, the relationship between H. pylori and reflux remains uncertain. The aim of this study was to investigate this relationship in a population-based, nested, case-control study. METHODS: From a cohort of 65,363 individuals, representing 71.2% of the adult population in the Norwegian county of Nord-Trondelag, we randomly selected 472 persons with recurrent reflux symptoms (cases) and 472 without such symptoms (controls). Occurrence of H. pylori and its virulence factor cagA was determined serologically, using an immunoblot assay. Gastric atrophy was assessed through serum levels of pepsinogen I. Odds ratios (OR) with 95% confidence intervals (CI), adjusted for potential confounding factors, represented relative risks. RESULTS: H. pylori infection was not associated with a decreased risk of reflux symptoms (OR 1.1, 95% CI 0.8-1.6), irrespective of positive cagA status (OR 1.1, 95% CI 0.8-1.5). Gastric atrophy reduced the risk of reflux symptoms (OR 0.2, 95% CI 0.0-0.6). Infection with H. pylori entailed a ninefold increase in the risk of gastric atrophy compared to non-infection (OR 8.9, 95% CI 2.0-39.9). CONCLUSIONS: H. pylori infection, irrespective of cagA status, did not affect the occurrence of reflux symptoms in this population-based setting. Infected individuals are at increased risk of gastric atrophy, which in turn reduces reflux symptoms, but due to the low frequency of gastric atrophy among infected individuals overall, there was no association with reflux symptoms on a population level.     

Quantitative proteomic assessment of very early cellular signaling events

Technical limitations have prevented proteomic analyses of events occurring less than 30 s after signal initiation. We developed an automated, continuous quench-flow system allowing quantitative proteomic assessment of very early cellular signaling events (qPACE) with a time resolution of 1 s. Using this technique, we determined that autophosphorylation of the epidermal growth factor receptor occurs within 1 s after ligand stimulation and is followed rapidly by phosphorylation of the downstream signaling intermediates Src homologous and collagen-like protein and phospholipase C gamma 1.     

Effects of snow cover on the timing and success of reproduction in high-Arctic pink-footed geese <Emphasis Type="Italic">Anser brachyrhynchus</Emphasis>

During four breeding seasons, 2003–2006, we studied the relationship between snow cover and nesting performance in pink-footed geese (Anser brachyrhynchus) in a key breeding site on Svalbard. Snow cover in late May, i.e., at the time of egg laying of geese, was derived from MODIS satellite images. Snow cover had a profound cascading effect on reproductive output via the number of nesting pairs and timing of nesting, which affected nest success, while there was only a tendency for a negative effect on clutch size. Hence, we estimated a five-fold difference in the number of young produced (to post-hatching) between years with little snow and years with high snow cover. The results from the study area correlated with whole-population productivity estimates recorded in autumn. Thus, snow cover derived from MODIS satellite images appears to provide a useful indicator of the breeding conditions in the Arctic.     

Analysis of gene order data supports vertical inheritance of the leukotoxin operon and genome rearrangements in the 5' flanking region in genus <Emphasis Type="Italic">Mannheimia</Emphasis>

Background  

The Mannheimia subclades belong to the same bacterial genus, but have taken divergent paths toward their distinct lifestyles. For example, M. haemolytica + M. glucosida are potential pathogens of the respiratory tract in the mammalian suborder Ruminantia, whereas M. ruminalis, the supposed sister group, lives as a commensal in the ovine rumen. We have tested the hypothesis that vertical inheritance of the leukotoxin (lktCABD) operon has occurred from the last common ancestor of genus Mannheimia to any ancestor of the diverging subclades by exploring gene order data.     

Dual-probe system using pyrenylmethyl-modified amino-LNA for mismatch detection

A dual-probe containing pyrenylmethyl amino-LNA has been developed for sensitive mismatch detection. While hybridization with complementary DNA/RNA results in very strong excimer signals, exposure to singly mismatched DNA/RNA targets results in significantly decreased excimer emission.