DYNAVAX TECHNOLOGIES CORPORATION : Dynavax Initiates First Human … – 4-traders (press release)

DYNAVAX TECHNOLOGIES CORPORATION : Dynavax Initiates First Human
4-traders (press release)
BERKELEY, CA — (Marketwired) — 10/09/13 — Dynavax Technologies Corporation (NASDAQ: DVAX) announced today the start of dosing in the first human clinical trial in its asthma program. Dynavax is conducting the trial under its collaboration agreement 
Dynavax starts Phase I trial of asthma treatmentSan Francisco Business Times (blog)
Dynavax Initiates First Human Trial in Asthma ProgramMENAFN.COM

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Genetic Variant Increases Asthma Risk in Children With Human Rhinovirus – Monthly Prescribing Reference

Genetic Variant Increases Asthma Risk in Children With Human Rhinovirus
Monthly Prescribing Reference
Minal Caliskan, from University of Chicago, and colleagues genotyped the 17q21 locus. Associations between asthma and HRV and respiratory syncytial virus (RSV) wheezing illness were assessed. Both unstimulated and HRV-stimulated peripheral-blood

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Comprehensive FISH Probe Design Tool Applied to Imaging Human Immunoglobulin Class Switch Recombination.

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Comprehensive FISH Probe Design Tool Applied to Imaging Human Immunoglobulin Class Switch Recombination.

PLoS One. 2012;7(12):e51675

Authors: Nedbal J, Hobson PS, Fear DJ, Heintzmann R, Gould HJ

Abstract
We present a web engine boosted fluorescence in-situ hybridization (webFISH) algorithm using a genome-wide sequence similarity search to design target-specific single-copy and repetitive DNA FISH probes. The webFISH algorithm featuring a user-friendly interface (http://www.webfish2.org/) maximizes the coverage of the examined sequences with FISH probes by considering locally repetitive sequences absent from the remainder of the genome. The highly repetitive human immunoglobulin heavy chain sequence was analyzed using webFISH to design three sets of FISH probes. These allowed direct simultaneous detection of class switch recombination in both immunoglobulin-heavy chain alleles in single cells from a population of cultured primary B cells. It directly demonstrated asynchrony of the class switch recombination in the two alleles in structurally preserved nuclei while permitting parallel readout of protein expression by immunofluorescence staining. This novel technique offers the possibility of gaining unprecedented insight into the molecular mechanisms involved in class switch recombination.

PMID: 23272136 [PubMed – in process]

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IL-13 exposure enhances vitamin D-mediated expression of the human cathelicidin antimicrobial peptide-hCAP18/LL-37 in bronchial epithelial cells.

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IL-13 exposure enhances vitamin D-mediated expression of the human cathelicidin antimicrobial peptide-hCAP18/LL-37 in bronchial epithelial cells.

Infect Immun. 2012 Oct 8;

Authors: Schrumpf JA, van Sterkenburg MA, Verhoosel RM, Zuyderduyn S, Hiemstra PS

Abstract
Vitamin D is an important regulator of the expression of antimicrobial peptides, and vitamin D deficiency is associated with respiratory infections. Regulating expression of antimicrobial peptides such as the human cathelicidin antimicrobial peptide (hCAP)18/LL-37 by vitamin D in bronchial epithelial cells requires local conversion of 25(OH)vitaminD(3) (25D(3)) into its bioactive metabolite 1,25(OH)(2)vitaminD(3) (1,25D(3)) by CYP27B1. Low circulating vitamin D-levels in childhood asthma are associated with more severe exacerbations, which are often associated with infections. Atopic asthma is accompanied by Th2 driven inflammation mediated by cytokines such as IL-4 and IL-13, and the effect of these cytokines on vitamin D metabolism and hCAP-18/LL-37 expression is unknown. Therefore we investigated this in well-differentiated bronchial epithelial cells. To this end, cells were treated with IL-13 with and without 25D(3) and expression of hCAP18/LL-37, CYP27B1, the 1,25D(3) inactivating enzyme CYP24A1, and vitamin D receptor was assessed by quantitative PCR. We show that IL-13 enhances the ability of 25D(3) to increase expression of hCAP18/LL-37 and CYP24A1. In addition, exposure to IL-13 resulted in increased CYP27B1 expression, whereas VDR expression was not significantly affected. The enhancing effect of IL-13 on 25D(3)-mediated expression of hCAP18/LL-37 was further confirmed using SDS-PAGE Western Blot and immunofluorescence staining. In conclusion, we demonstrate that IL-13 induces vitamin D(-)dependent hCAP18/LL-37 expression, most likely by increasing CYP27B1. These data suggest that Th2 cytokines regulate the vitamin D metabolic pathway in bronchial epithelial cells.

PMID: 23045480 [PubMed – as supplied by publisher]

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EPA’s Human Experiments, Salmonella Scare and Terrorists Extradited to U.S. – Patch.com

EPA's Human Experiments, Salmonella Scare and Terrorists Extradited to U.S.
Patch.com
"It is extremely disturbing that EPA may have conducted illegal human experiments, exposing people with conditions such as asthma and metabolic syndrome to concentrated high levels of substances like fine particulate matter and diesel exhaust," Inhofe
Lawmaker wants probe of EPA experiments on humansFox News

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Distribution of polymorphisms IL4-590 C/T and IL4 RP2 in the human populations of Madeira, Azores, Portugal, Cape Verde and Guinea-Bissau.

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Distribution of polymorphisms IL4-590 C/T and IL4 RP2 in the human populations of Madeira, Azores, Portugal, Cape Verde and Guinea-Bissau.

Int J Mol Epidemiol Genet. 2012;3(2):179-83

Authors: Berenguer AG, C�¢mara RA, Brehm AD, Oliveira S, Fernandes AT

Abstract
The IL4 gene is located on chromosome 5q23.3-31.2. Polymorphisms within this cytokine gene, like the derivative allele T of IL4-590, have been reported as being associated to elevated IgE serum levels and asthma. In the present work, the allelic and genotypic frequency of the IL4-590 and IL4 RP2 polymorphisms was carried out in 599 individuals from Madeira, Azores, Portugal mainland, Cape Verde and Guinea-Bissau and in a sample of 101 asthmatics from Madeira population. In all populations the polymorphisms were in LD and presented a significant dissimilar allelic and genotypic distribution (p<0.05) except between mainland Portugal and Madeira when compared to Azores. Significant differences regarding both loci were found between Madeira population and the group of asthmatics. Genotype 183183TT frequency is higher for African populations while 253253CC prevails in Caucasian populations. The existence of a Hardy-Weinberg Disequilibrium in Guinea-Bissau population not observed in neutral markers leads to the hypothesis of natural selection occurring in these loci probably associated to a rapid population growth an hypothesis strengthened by neutral STRs D5S818 and CSF1PO gene diversity.

PMID: 22724055 [PubMed – in process]

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Updates in the relationship between human rhinovirus and asthma.

Updates in the relationship between human rhinovirus and asthma.

Allergy Asthma Immunol Res. 2012 May;4(3):116-21

Authors: Kim WK, Gern JE

Abstract
Human rhinovirus (HRV) is a nonenveloped, single stranded RNA virus belonging to the family Picornaviridae. HRV infections can cause both upper and lower respiratory illnesses in children and adults. Lower respiratory illnesses are more likely to occur in specific high risk groups, including infants, and children and adults with asthma. The relationships between rates of infection and the risk of clinical illness and exacerbation are not completely understood. Recent studies employing polymerase chain reaction and other molecular techniques indicate that there are new branches on the HRV family tree, and one characteristic of recently detected viruses is that they cannot be detected by standard tissue culture. Here we review the current literature and discuss new advances in understanding the link between HRV and asthma.

PMID: 22548203 [PubMed – in process]

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