Beta2 Adrenergic Receptor (ADRβ2) Haplotype Pair (2/4) Is Associated with Severe Asthma

Background

β2 adrenergic receptor (ADRβ2) polymorphisms including ADRβ2+46G>A have been reported to cause adverse outcomes in mild asthmatics. The extent to which ADRβ2 polymorphisms and in particular their haplotypes contribute to severe asthma is unknown.

Objective

To determine the association of ADRβ2 polymorphisms and haplotypes with asthma severity.

Methods

Caucasians (n = 2979) were genotyped for 11 ADRβ2 polymorphisms. The cohort (mean age 39.6, 60% female) included 2296 non-asthmatics, 386 mild asthmatics, 172 moderate asthmatics and 125 severe asthmatics. Haplotype frequency and haplotype pair for each subject was determined using the PHASE algorithm.

Results

The three asthmatic cohorts were comparable in age and gender but were distinguishable from each other in terms of symptoms, spirometry, medication use and health care utilisation (p <0.001). None of the polymorphisms showed a genotypic or allelic association with asthma diagnosis or severity. Nine haplotypes were identified and no association was found with asthma diagnosis or severity per se. Haplotype pair 2/4 was associated with asthma severity (Trend Test, OR 1.42, p = 0.0008) but not with asthma per se. Prevalence of haplotype pair 2/2 appeared to decrease with asthma severity (Trend Test, OR 0.78, p = 0.067). Two new haplotypes were identified, occurring exclusively in asthmatics at a frequency of ≥ 1%. In addition, a positive association between carriage of ADRβ2 +523*C and increased risk of atopy was discovered.

Conclusions

ADRβ2 haplotype pair 2/4 is associated with severe asthma and is consistent with findings of poor bronchodilator response in mild asthmatics who are also haplotype 2/4.     

Potential use of loss of heterozygosity in pleural effusions of breast cancer metastases using the microsatellite marker of the 16q22.1 region of the CDH1 gene

OBJECTIVE: To evaluate the presence of allelic loss in 16q22.1, including the locus of E-cadherin, in pleural effusions in breast cancer patients. STUDY DESIGN: Molecular analysis of DNA was performed using a DNA extraction kit (NucleoSpin, Macherey-Nagel, Germany). Loss of heterozygosity (LOH) in primary tumors and pleural effusions was analyzed using a microsatellite marker of the CDH1 gene, D16S265, described in previous studies. LOH was evaluated by radioactive polymerase chain reaction assay in 17 samples of pleural effusions and breast tissues (primary tumors and nonneoplastic adjacent tissue) from breast cancer patients: 7 positive for neoplastic cells, 6 suspected and 4 cases without evidence of neoplastic cells in the effusions. RESULTS: Thirteen cases (76%) were informative. LOH was detected in 5 cases (38.5%). In 3 of them LOH was detected only in the cytologic sample, and in 2 of them LOH was detected in the primary tumor and cytologic sample. CONCLUSION: Results show that LOH in the CDH1 gene can identify tumor cells in pleural effusions when morphologic analysis is difficult.     

Use of the paired samples (cerebrospinal fluid and serum) in immunodiagnostic of active and inactive human neurocysticercosis

Paired samples of cerebrospinal fluid (CSF) and serum of 30 patients--10 with active, 10 with inactive neurocysticercosis (NCC), and 10 control subjects--were evaluated by enzyme-linked immunosorbent assay (ELISA) using two Taenia crassiceps metacestode extracts as antigen in order to detect IgG antibodies. In active NCC, high levels of IgG were detected (p < 0.05). The CSF samples showed 80% (CI 72-88) of reactivity in the saline extract (S) and 90% (CI 84-95) in sodium dodecyl sulphate (SDS) and the serum samples were reactive in 90% (CI 84-95) and 100% (CI 98-100) in the S and SDS antigenic extracts, respectively. The use of the paired samples of CSF and serum in active NCC showed equivalent results suggesting that the serum samples could be used as a screening in those patients whose CSF puncture is counter-indicated.     

Recombinant Escherichia coli heat-labile enterotoxin B subunit humoral adjuvant effect depends on dose and administration route

Information on the use of Escherichia coli heat-labile enterotoxin B subunit (LTB) as a parenteral adjuvant is scarce. We evaluate the adjuvant effect of different concentrations of recombinant LTB (rLTB), as well as the influence of administration route (intramuscular and subcutaneous) on mice immune response. The use of 10 μg/dose of rLTB as adjuvant of an inactivated vaccine composed by Suid herpesvirus type 1 (SuHV-1), used to immunize mice intramuscularly, induced the highest average titers of anti-SuHV-1 antibodies (P < 0.05). The same vaccines used subcutaneously induced lower titers of antibodies. The lower the anti-rLTB humoral response determined by ELISA, the higher was its adjuvant activity. In the challenge experiment with SuHV-1, 56% (14/25) (P < 0.05) of the animals inoculated intramuscularly and 32% (8/25) inoculated subcutaneously survived, highlighting the influence of the concentration and the route of administration of rLTB on its performance as an adjuvant. Therefore, rLTB can significantly help in the induction of immunity against SuHV-1 in mice, especially if used intramuscularly in the concentration of 10 μg/dose, representing the best cost-benefit ratio.     

Selection of nest sites by wood mice Apodemus sylvaticus in a Mediterranean agro-forest landscape

One of the most important structures for an individual’s survival is a refuge, especially for species subject to significant predatory pressure or living in environments affected by severe climatic conditions. We studied how wood mice (Apodemus sylvaticus), inhabiting a Mediterranean environment, use nests and the factors that could be determining this use. Radio-tracking of 16 mice allowed us to detect 24 diurnal nests, which were used with a high fidelity rate (1.75 nests/animal). Nest sites that had been identified using radio-tracking were matched with 24 randomly selected non-nest sites (located within an area defined by the sum of all individual home ranges), and all sites were characterized according to their macro- and micro-habitat parameters. Using a generalized linear model, we tested three hypotheses: (1) a nest’s use is influenced by its proximity to food patches; (2) the degree of sheltering provided by each site influences its use; and (3) nest use is constrained by a combination of food- and shelter-related features. Females had higher nest fidelity than males, and the degree of sheltering provided by each site had a positive significant influence on its use. Nests offering higher protection (e.g., under thick vegetation), good drainage (e.g., sleep slopes), and lower human and predatory disturbance (far from orchards) were most often used. The proximity to food patches seemed to negatively influence nest use. Results indicate the need to preserve patches of natural dense vegetation near riparian habitats, which is in agreement with the focus of mammalian protection plans in Mediterranean agricultural landscapes. These patches are important areas for Apodemus sylvaticus, an acorn disperser species, which is preyed on by raptors and mammalian carnivores.     

How prevalent are Plasmodium ovale and P. malariae in East Asia?

Plasmodium ovale and Plasmodium malariae, two of the four human malaria parasites, are usually found at very low prevalence in East Asia, even in areas with intense malaria transmission. In this article, Fumihiko Kawamoto, Qing Liu, Marcelo Ferreira and Indah Tantular review data obtained in recent field surveys, using alternative diagnostic methods such as acridine orange staining and PCR-based methods, to evaluate the prevalence of these two malaria species in East Asia. They argue that these species might be much more prevalent in East Asia than reported previously. In addition, they discuss the implications of sequence variations found in the small subunit ribosomal RNA genes of the two species targeted by diagnostic PCR and compare morphological criteria for speciation of malaria parasites stained with Giemsa and acridine orange.     

Nitrogen-fixing bacteria communities occurring in soils under different uses in the Western Amazon Region as indicated by nodulation of siratro (Macroptilium atropurpureum)

Understanding native communities is a crucial step for the management of biological nitrogen fixation, since they may be either a source of efficient strains or a limiting factor when efficient strains need to be introduced. This work aimed to evaluate the density, diversity and efficiency of Leguminosae nodulating bacterial (LNB) communities and their component strains in soils under various land use systems (LUSs): pristine forest, agriculture, pasture, agroforestry, young secondary forest, and old secondary forest,. The LNB communities were trapped from these soils by using the promiscuous host siratro under controlled conditions. We also studied their relationships with physical and chemical attributes of the soil. Agroforestry and agriculture soil samples induced the highest number of nodules in siratro, while forest soil samples induced the lowest number of nodules. No relationship was found between LNB and Leguminosae species diversity in the LUSs. The soil chemical variables that were most related to differences in nodule number and shoot dry matter weight of plants inoculated with soil suspensions of the LUSs were, respectively: Ca²⁺, Mg²⁺, base saturation, exchangeable bases and Cu²⁺; and pH, cation exchange capacity, B, Cu²⁺ and clay. Although, LNB communities from all LUSs were efficient under controlled and similar conditions, they were found to be composed of strains with variable efficiency: inefficient, efficient, highly efficient and superior efficiency. Efficient strains occurred at the highest frequency in all LUSs. The isolated strains presented similar and new sequences that were phylogenetically related to well known LNB genera in α-and β-Proteobacteria. Unusual genera in these branches, as well as in other branches, which are probably endophytic bacteria, were also isolated from nodules. These data support siratro as a useful trap species to study the LNB biodiversity of diverse ecosystems in tropical soils. The fact that the highest diversity and nodulation were seen in managed systems such as agriculture and agroforestry suggests a high resilience of LNB communities to changes in land use after deforestation in a region where large forest areas are still preserved and can be a source of propagules.