Breathe Well Live Well
Lancashire Evening Post |
Gene breakthrough offers hope to asthma sufferers
Lancashire Evening Post Dr da Silva said: “Alternative therapeutic approaches that can both reduce inflammatory and remodeling processes by over-expressing or inhibiting specific genes in the asthma inflammatory cascade, in different types of asthma and without leading to … |
View full post on asthma – Google News
The Star |
Gene breakthrough hope for South Yorkshire asthma sufferers
The Star A new gene therapy which could reduce inflammation Sheffield asthma sufferers' lungs is on the horizon offering hope to millions of patients. A study showed the gene therapy dramatically boosted the working of patients' lungs. Asthma affects 5.5 … |
View full post on asthma – Google News
|
Novel gene therapy shows potential for lung repair in asthma
Science Daily In asthma, airways become inflamed, resulting in narrowing of these airways and debilitating symptoms that include coughing, wheezing, shortness of breath and chest tightness. Asthma and other respiratory diseases also cause changes in the large and … |
View full post on asthma – Google News
|
Nanoparticle-based gene therapy may hold promise for patients with asthma
News-Medical.net A new study has demonstrated a way to deliver a nanoparticle-based gene therapy, in order to repair lungs damaged by chronic allergic asthma and to reduce inflammation that causes asthma attacks. The potential therapy, tested in mice, may hold promise … |
View full post on asthma – Google News
EurekAlert (press release) |
Novel gene therapy shows potential for lung repair in asthma American Thoracic Society
EurekAlert (press release) ATS 2016, SAN FRANCISCO — A new study has demonstrated a way to deliver a nanoparticle-based gene therapy, in order to repair lungs damaged by chronic allergic asthma and to reduce inflammation that causes asthma attacks. The potential therapy … |
View full post on asthma – Google News
 |
Related Articles |
Identifying Mutations of the Tetratricopeptide Repeat Domain 37 (TTC37) Gene in Infants With Intractable Diarrhea and a Comparison of Asian and Non-Asian Phenotype and Genotype: A Global Case-report Study of a Well-Defined Syndrome With Immunodeficiency.
Medicine (Baltimore). 2016 Mar;95(9):e2918
Authors: Lee WI, Huang JL, Chen CC, Lin JL, Wu RC, Jaing TH, Ou LS
Abstract
Syndromic diarrhea/tricho-hepato-enteric syndrome (SD/THE) is a rare, autosomal recessive and severe bowel disorder mainly caused by mutations in the tetratricopeptide repeat domain 37 (TTC37) gene which act as heterotetrameric cofactors to enhance aberrant mRNAs decay. The phenotype and immune profiles of SD/THE overlap those of primary immunodeficiency diseases (PIDs).Neonates with intractable diarrhea underwent immunologic assessments including immunoglobulin levels, lymphocyte subsets, lymphocyte proliferation, superoxide production, and IL-10 signaling function. Candidate genes for PIDs predisposing to inflammatory bowel disease were sequencing in this study.Two neonates, born to nonconsanguineous parents, suffered from intractable diarrhea, recurrent infections, and massive hematemesis from esopharyngeal varices due to liver cirrhosis or accompanying Trichorrhexis nodosa that developed with age and thus guided the diagnosis of SD/THE compatible to TTC37 mutations (homozygous DelK1155H, Fs*2; heterozygous Y1169Ter and InsA1143, Fs*3). Their immunologic evaluation showed normal mitogen-stimulated lymphocyte proliferation, superoxide production, and IL-10 signaling, but low IgG levels, undetectable antibody to hepatitis B surface antigen and decreased antigen-stimulated lymphocyte proliferation. A PubMed search for bi-allelic TTC37 mutations and phenotypes were recorded in 14 Asian and 12 non-Asian cases. They had similar presentations of infantile onset refractory diarrhea, facial dysmorphism, hair anomalies, low IgG, low birth weight, and consanguinity. A higher incidence of heart anomalies (8/14 vs 2/12; P?=?0.0344, Chi-square), nonsense mutations (19 in 28 alleles), and hot-spot mutations (W936Ter, 2779-2G>A, and Y1169Ter) were found in the Asian compared with the non-Asian patients. Despite immunoglobulin therapy in 20 of the patients, 4 died from liver cirrhosis and 1 died from sepsis.Patients of all ethnicities with SD/THE with the characteristic triad of T nodosa, hepatic cirrhosis, and intractable enteropathy have low IgG, poor vaccine response and/or decreased antigen-stimulated lymphocyte proliferation. This is now better classified into the subgroup of “well-defined syndromes with immunodeficiency” (the update termed as “combined immunodeficiencies with associated or syndromic features”) than “predominantly antibody deficiencies” in the update PIDs classification, and requires optimal interventions.
PMID: 26945392 [PubMed – in process]
View full post on pubmed: asthma
Differential gene network analysis for the identification of asthma-associated therapeutic targets in allergen-specific T-helper memory responses.
BMC Med Genomics. 2016;9(1):9
Authors: Troy NM, Hollams EM, Holt PG, Bosco A
Abstract
BACKGROUND: Asthma is strongly associated with allergic sensitization, but the mechanisms that determine why only a subset of atopics develop asthma are not well understood. The aim of this study was to test the hypothesis that variations in allergen-driven CD4 T cell responses are associated with susceptibility to expression of asthma symptoms.
METHODS: The study population consisted of house dust mite (HDM) sensitized atopics with current asthma (n?=?22), HDM-sensitized atopics without current asthma (n?=?26), and HDM-nonsensitized controls (n?=?24). Peripheral blood mononuclear cells from these groups were cultured in the presence or absence of HDM extract for 24 h. CD4 T cells were then isolated by immunomagnetic separation, and gene expression patterns were profiled on microarrays.
RESULTS: Differential network analysis of HDM-induced CD4 T cell responses in sensitized atopics with or without asthma unveiled a cohort of asthma-associated genes that escaped detection by more conventional data analysis techniques. These asthma-associated genes were enriched for targets of STAT6 signaling, and they were nested within a larger coexpression module comprising 406 genes. Upstream regulator analysis suggested that this module was driven primarily by IL-2, IL-4, and TNF signaling; reconstruction of the wiring diagram of the module revealed a series of hub genes involved in inflammation (IL-1B, NFkB, STAT1, STAT3), apoptosis (BCL2, MYC), and regulatory T cells (IL-2Ra, FoxP3). Finally, we identified several negative regulators of asthmatic CD4 T cell responses to allergens (e.g. IL-10, type I interferons, microRNAs, drugs, metabolites), and these represent logical candidates for therapeutic intervention.
CONCLUSION: Differential network analysis of allergen-induced CD4 T cell responses can unmask covert disease-associated genes and pin point novel therapeutic targets.
PMID: 26922672 [PubMed – as supplied by publisher]
View full post on pubmed: asthma
Relation between sonic hedgehog pathway gene polymorphisms and basal cell carcinoma development in the Polish population.
Arch Dermatol Res. 2015 Nov 21;
Authors: Lesiak A, Sobolewska-Sztychny D, Majak P, Sobjanek M, Wodz K, Sygut KP, Majsterek I, Wozniacka A, Narbutt J
Abstract
In recent decades, increases have been observed in the incidence of nonmelanoma skin cancers, including basal cell carcinoma (BCC) and squamous cell carcinoma. BCC is the most common neoplasm in Caucasian populations. Sonic hedgehog (Shh) pathway impairment plays a key role in BCC pathogenesis, and there is evidence that Shh pathway genetic variations may predispose to BCC development. We genotyped 22 single-nucleotide polymorphisms (SNPs) in 4 Shh pathway genes: SHH, GLI, SMO, and PTCH. The study group consisted of 142 BCC patients and 142 age-matched, sex-matched healthy subjects (controls). SNPs were assessed using the PCR-RFLP method. The genotype distribution for the polymorphisms in the rs104894049 331 A/T SHH, rs104894040 349 T/C SHH, and rs41303402 385 G/A SMO genes differed significantly between the BCC patients and the controls. The presence of CC genotype in the SHH rs104894040 349 T/C polymorphism was linked to the highest risk of BCC development (OR 87.9, p < 0.001). Other genotypes, such as the TT in SHH rs104894049 331 A/T and the GG in SMO rs41303402 385 G/A also statistically raised the risk of BCC, but these associations were weaker. Other investigated polymorphisms showed no statistical differences between patients and controls. The results obtained testify to the importance of the SHH and SMO gene polymorphisms in skin cancerogenesis. These results mainly underline the potential role of SHH3 rs104894040 349 T/C gene polymorphism in the development of skin basal cell carcinomas in patients of Polish origin.
PMID: 26590974 [PubMed – as supplied by publisher]
View full post on pubmed: asthma
|
NEW ASTHMA GENE IDENTIFIED
HealthCanal.com Scientists at QIMR Berghofer Medical Research Institute have found that a gene previously thought to have an anti-inflammatory effect, or no immune effect at all, is actually more likely to increase inflammation in people with asthma and allergies. Dr … |
View full post on asthma – Google News
The Australian (blog) |
Asthma: Australian researchers find PAG1 gene may be linked | The Australian
The Australian (blog) While previous discoveries by Dr Ferreira led to a current clinical trial testing whether a drug used to treat rheumatoid arthritis could be useful in treating asthma, he cautioned that further research was needed to determine the potential impact of … |
View full post on asthma – Google News