Children with stable asthma have reduced airway matrix metalloproteinase-9 and matrix metalloproteinase-9/tissue inhibitor of metalloproteinase-1 ratio

Background Childhood asthma is characterized by inflammation of the airways. Structural changes of the airway wall may also be seen in some children early in the course of the disease. Matrix metalloproteinases (MMPs) are key mediators in the metabolism of the extracellular matrix (ECM). Objective To investigate the balance of MMP-8, MMP-9 and tissue inhibitor of metalloproteinases (TIMP)-1 in the airways of children with asthma. Methods One hundred and twenty-four children undergoing elective surgical procedures also underwent non-bronchoscopic bronchoalveolar lavage (BAL). MMP-8, MMP-9 and TIMP-1 were measured by ELISA. Results There was a significant reduction in MMP-9 in atopic asthmatic children (n=31) compared with normal children (n=30) [median difference: 0.57 ng/mL (95% confidence interval: 0.18–1.1 ng/mL)]. The ratio of MMP-9 to TIMP-1 was also reduced in asthmatic children. Levels of all three proteins were significantly correlated to each other and to the relative proportions of particular inflammatory cells in BAL fluid (BALF). Both MMP-8 and MMP-9 were moderately strongly correlated to the percentage neutrophil count (r=0.40 and 0.47, respectively, P

Toxicity of non-abeta component of Alzheimer's disease amyloid, and N-terminal fragments thereof, correlates to formation of beta-sheet structure and fibrils.

Synucleins are small proteins that are highly expressed in brain tissue and are localised at presynaptic terminals in neurons. alpha-Synuclein has been identified as a component of intracellular fibrillar protein deposits in several neurodegenerative diseases, and two mutant forms of alpha-synuclein have been associated with autosomal-dominant Parkinson's Disease. A fragment of alpha-synuclein has also been identified as the non-Abeta component of Alzheimer's Disease amyloid. In this review we describe some structural properties of alpha-synuclein and the two mutant forms, as well as alpha-synuclein fragments, with particular emphasis on their ability to form beta-sheet on ageing and aggregate to form amyloid-like fibrils. Differences in the rates of aggregation and morphologies of the fibrils formed by alpha-synuclein and the two mutant proteins are highlighted. Interactions between alpha-synuclein and other proteins, especially those that are components of amyloid or Lewy bodies, are considered. The toxicity of alpha-synuclein and related peptides towards neurons is also discussing in relation to the aetiology of neurodegenerative diseases.

Components of resistance to Fusarium head blight in wheat detected in a seed germination assay with Microdochium majus and the relationship to FHB disease development and mycotoxin accumulation from Fusarium graminearum infection.

Components of partial disease resistance (PDR) to fusarium head blight (FHB), detected in a seed-germination assay, were compared with whole-plant FHB resistance of 30 USA soft red winter wheat entries in the 2002 Uniform Southern FHB Nursery. Highly significant (P <0·001) differences between cultivars in the in vitro seed-germination assay inoculated with Microdochium majus were correlated to FHB disease incidence (r = -0·41; P <0·05), severity (r = -0·47; P <0·01), FHB index (r = -0·46; P <0·01), damaged kernels (r = -0·52; P <0·01), grain deoxynivalenol (DON) concentration (r = -0·40; P <0·05) and incidence/severity/kernel-damage index (ISK) (r = -0·45; P <0·01) caused by Fusarium graminearum. Multiple linear regression analysis explained a greater percentage of variation in FHB resistance using the seed-germination assay and the previously reported detached-leaf assay PDR components as explanatory factors. Shorter incubation periods, longer latent periods, shorter lesion lengths in the detached-leaf assay and higher germination rates in the seed-germination assay were related to greater FHB resistance across all disease variables, collectively explaining 62% of variation for incidence, 49% for severity, 56% for F. graminearum-damaged kernels (FDK), 39% for DON and 59% for ISK index. Incubation period was most strongly related to disease incidence and the early stages of infection, while resistance detected in the seed germination assay and latent period were more strongly related to FHB disease severity. Resistance detected using the seed-germination assay was notable as it related to greater decline in the level of FDK and a smaller reduction in DON than would have been expected from the reduction in FHB disease assessed by visual symptoms.

Safety and Immunogenicity of a Novel Recombinant Subunit Respiratory Syncytial Virus Vaccine (BBG2Na) in Healthy Young Adults

A novel recombinant respiratory syncytial virus (RSV) subunit vaccine, designated BBG2Na, was administered to 108 healthy adults randomly assigned to receive 10, 100, or 300 μg of BBG2Na in aluminum phosphate or saline placebo. Each subject received 1, 2, or 3 intramuscular injections of the assigned dose at monthly intervals. Local and systemic reactions were mild, and no evidence of harmful properties of BBG2Na was reported. The highest ELISA and virus-neutralizing (VN) antibody responses were evident in the 100- and 300-μg groups; second or third injections provided no significant boosts against RSV-derived antigens. BBG2Na induced ⩾2-fold and ⩾4-fold increases in G2Na-specific ELISA units in up to 100% and 57% of subjects, respectively; corresponding RSV-A–specific responses were 89% and 67%. Furthermore, up to 71% of subjects had ⩾2-fold VN titer increases. Antibody responses to 2 murine lung protective epitopes were also highly boosted after vaccination. Therefore, BBG2Na is safe, well tolerated, and highly immunogenic in RSV-seropositive adults

Association between polymorphism in regulatory region of gene encoding tumour necrosis factor alpha and risk of Alzheimer's disease and vascular dementia: a case-control study

BACKGROUND: Deposition of beta-amyloid in the brains of patients with Alzheimer's disease is thought to precede a chain of events that leads to an inflammatory response by the brain. We postulated that genetic variation in the regulatory region of the gene for the proinflammatory cytokine tumour necrosis factor alpha (TNF-alpha) leads to increased risk of Alzheimer's disease and vascular dementia. METHODS: A polymorphism in the regulatory region of the TNF-alpha gene was analysed in a case-control study. The polymorphism (C-850T) was typed in 242 patients with sporadic Alzheimer's disease, 81 patients with vascular dementia, 61 stroke patients without dementia, and 235 normal controls. These groups of individuals were also genotyped for the apolipoprotein E polymorphism, and the vascular dementia and stroke groups were typed at the HLA-DR locus. FINDINGS: The distribution of TNF-alpha genotypes in the vascular dementia group differed significantly from that in the stroke and normal control groups, giving an odds ratio of 2.51 (95% CI 1.49-4.21) for the development of vascular dementia for individuals with a CT or TT genotype. Logistic regression analysis indicated that the possession of the T allele significantly increased the risk of Alzheimer's disease associated with carriage of the apolipoprotein E epsilon4 allele (odds ratio 2.73 [1.68-4.44] for those with apolipoprotein E epsilon4 but no TNF-alpha T, vs 4.62 [2.38-8.96] for those with apolipoprotein E epsilon4 and TNF-alpha T; p=0.03). INTERPRETATION: Possession of the TNF-alpha T allele significantly increases the risk of vascular dementia, and increases the risk of Alzheimer's disease associated with apolipoprotein E. Although further research is needed, these findings suggest a potential role for anti-inflammatory therapy in vascular dementia and Alzheimer's disease, and perhaps especially in patients who have had a stroke.