A rare IL33 loss-of-function mutation reduces blood eosinophil counts and protects from asthma.

Efst á síðunni er hægt að nálgast greinina í heild sinni með því að smella á hlekkinnIL-33 is a tissue-derived cytokine that induces and amplifies eosinophilic inflammation and has emerged as a promising new drug target for asthma and allergic disease. Common variants at IL33 and IL1RL1, encoding the IL-33 receptor ST2, associate with eosinophil counts and asthma. Through whole-genome sequencing and imputation into the Icelandic population, we found a rare variant in IL33 (NM_001199640:exon7:c.487-1G>C (rs146597587-C), allele frequency = 0.65%) that disrupts a canonical splice acceptor site before the last coding exon. It is also found at low frequency in European populations. rs146597587-C associates with lower eosinophil counts (β = -0.21 SD, P = 2.5×10-16, N = 103,104), and reduced risk of asthma in Europeans (OR = 0.47; 95%CI: 0.32, 0.70, P = 1.8×10-4, N cases = 6,465, N controls = 302,977). Heterozygotes have about 40% lower total IL33 mRNA expression than non-carriers and allele-specific analysis based on RNA sequencing and phased genotypes shows that only 20% of the total expression is from the mutated chromosome. In half of those transcripts the mutation causes retention of the last intron, predicted to result in a premature stop codon that leads to truncation of 66 amino acids. The truncated IL-33 has normal intracellular localization but neither binds IL-33R/ST2 nor activates ST2-expressing cells. Together these data demonstrate that rs146597587-C is a loss of function mutation and support the hypothesis that IL-33 haploinsufficiency protects against asthma.Netherlands Asthma Foundation University Medical Center Groningen Ministry of Health and Environmental Hygiene of Netherlands Netherlands Asthma Stichting Astma Bestrijding BBMRI European Respiratory Society private and public research funds AstraZeneca ALK-Abello, Denmar

Uwalnianie alfa-amylazy przez komorki pecherzykowe izolowane z trzustek swinek morskich zarazonych inwazyjnymi jajami Ascaris suum

The studies were carried out on dispersed acini prepared from pancreas of guinea pigs infected with 5000 invasive eggs of Ascaris suum. The basal amylase secretion and that stimulated with acetylcholine and carbachol or blocked with atropine was determined. The basal secretion of amylase was significantly higher in pancreatic acini isolated from infected animals. The stimulation by acetylcholine and carbachol of these acini was weaker than in the control group. These results suggest that cholinergic stimulation of pancreatic amylase secretion was changed during larval ascaridosis

The activity of trypsin and alpha-amylase in pancreas of guinea pigs. IV. The influence of administration mixture of volatile organic acids, the invasive eggs of Ascaris suum, and homogenized eggs

The activity of alpha-amylase in the experimental groups of guinea pigs was lower than in control animals. The decreased level of activity of trypsin was noted (p<0.05) also in infected animals, and in treatment with organic acids. In the group of guinea pigs, which was administrated homogenized eggs of parasite, the activity of enzyme was a little higher than in control animals. The infection of animals was associated with increase of relative weight, of lungs. The guinea pigs treatment with organic acids had also a higher weight of spleen

The activity of trypsin and alpha-amylase in pancreas of guinea pigs. III. The influence of homogenized invasive eggs of Ascaris suum, and the mixture of organic acids C2-C6 on the activity of enzymes from pancreas extracts

The studies were carried out on pancreas extracts from guinea pigs free of parasite invasion. The activity of trypsin was determined according to the method of Anson, and amylase of Fennel method. The measurements of activity were done at the presence of homogenized invasive eggs of Ascaris suum, and the mixture of volatile organic acids C₂-C₆ (at concentrations of 30.3 and 0.3 mM/l). In samples with homogenized invasive eggs of A. suum the amylase activity remained unchanged while the activity of trypsin was considerably higher (p < 0,01). The introduction of the organic acids at conc. 30 mM/l into the samples was the reason of lower amylase activity. No influence of these acids on trypsin activity in pancreas extracts was observed

Owsica u dzieci przedszkolnych i szkolnych z wybranych placowek Olsztyna i jego okolicy

The studies were conducted during the school year of 1996/1997 among the children at the age of 5, 6 and 7 years old from Olsztyn and nearby municipality of Purda. In total, 151 children were examined by Graham's method. The presence of eggs of the parasite was confirmed in 13.3% of the total examined population. The infestation was tower in Olsztyn (12.0%) and the lowest in Purda (9.4%) but in the former state-owned Farm village Prajłowo it reached 27.8%. In general, the pinworms were found more frequently in 7 year old children (23.33%) than in case of the others (8.69% and 7.14% for 5 and 6 year old children respectively). In the study, younger boys were more frequently infested than the girls

The activity of hydrolases of entomopathogenic nematodes

Similar patterns of hydrolases were observed in three species representing two genera of entomopathogenic nematodes: Steinernema affinis, S. feltiae, and Heterorhabditis zealandica. The same enzymes were present in the studied nematodes but they differed in the level of activity of individual sub-classes of enzymes. A higher activity of esterases and proteolytic enzymes could be observed for H. zealandica than for S. affinis and S. feltiae. On the other hand, the activity of glycosidases in steinernematids was generally much higher than in H. Zealandica

The effect of vitamin A, B2 and B15 administration on the activity of alpha-amylase in lungs and kidney of guinea pig infected Ascaris suum

The guinea pigs were administrated vit. A (400 i.u.), vit. B₂ (1 mg) or vit. B₁₅ (5 mg). On the 9-th day of the experiment part of them was infectpd with 5000 invasive eggs of Ascaris suum. The invasion lasted 6 days and was controlled by lungs and kidney weight, and number of larvae in the lungs. The activity of amylase was determined by saccharogenic method in both organs. In the lungs of infected animals the activity of alpha-amylase was abouth 3 times lower than in the control. The infection of guinea pigs which were given vitamins did not cause change of enzyme's activity. In the kidney directive tendency was the same, but the differences were smaller. The infection resulted in an increase of relative mass of lungs. This index and number of larvae was considerable smaller in guinea pigs with vitamins A and B₁₅ administration. Any testing agent did not cause change of relative weight of kidney