Cancer risk in hospitalised asthma patients

Asthma is an increasingly common disorder, affecting 5–10% of the population. It involves a dysregulated immune function, which may predispose to subsequent cancer. We examined cancer risk among Swedish subjects who had hospital admission once or multiple times for asthma. An asthma research database was created by identifying asthma patients from the Swedish Hospital Discharge Register and by linking them with the Cancer Registry. A total of 140 425 patients were hospitalised for asthma during 1965–2004, of whom 7421 patients developed cancer, giving an overall standardised incidence ratio (SIR) of 1.36. A significant increase was noted for most sites, with the exception of breast and ovarian cancers and non-Hodgkin's lymphoma and myeloma. Patients with multiple hospital admissions showed a high risk, particularly for stomach (SIR 1.70) and colon (SIR 1.99) cancers. A significant decrease was noted for endometrial cancer and skin melanoma. Oesophageal and lung cancers showed high risks throughout the study period, whereas stomach cancer increased towards the end of the period. The relatively stable temporal trends suggest that the asthmatic condition rather than its medication is responsible for the observed associations

Risks of myeloid malignancies in patients with autoimmune conditions

Autoimmune conditions are associated with an elevated risk of lymphoproliferative malignancies, but few studies have investigated the risk of myeloid malignancies. From the US Surveillance Epidemiology and End Results (SEER)-Medicare database, 13 486 myeloid malignancy patients (aged 67+ years) and 160 086 population-based controls were selected. Logistic regression models adjusted for gender, age, race, calendar year and number of physician claims were used to estimate odds ratios (ORs) for myeloid malignancies in relation to autoimmune conditions. Multiple comparisons were controlled for using the Bonferroni correction (P<0.0005). Autoimmune conditions, overall, were associated with an increased risk of acute myeloid leukaemia (AML) (OR 1.29) and myelodysplastic syndrome (MDS, OR 1.50). Specifically, AML was associated with rheumatoid arthritis (OR 1.28), systemic lupus erythematosus (OR 1.92), polymyalgia rheumatica (OR 1.73), autoimmune haemolytic anaemia (OR 3.74), systemic vasculitis (OR 6.23), ulcerative colitis (OR 1.72) and pernicious anaemia (OR 1.57). Myelodysplastic syndrome was associated with rheumatoid arthritis (OR1.52) and pernicious anaemia (OR 2.38). Overall, autoimmune conditions were not associated with chronic myeloid leukaemia (OR 1.09) or chronic myeloproliferative disorders (OR 1.15). Medications used to treat autoimmune conditions, shared genetic predisposition and/or direct infiltration of bone marrow by autoimmune conditions, could explain these excess risks of myeloid malignancies

A Novel Protein LZTFL1 Regulates Ciliary Trafficking of the BBSome and Smoothened

Many signaling proteins including G protein-coupled receptors localize to primary cilia, regulating cellular processes including differentiation, proliferation, organogenesis, and tumorigenesis. Bardet-Biedl Syndrome (BBS) proteins are involved in maintaining ciliary function by mediating protein trafficking to the cilia. However, the mechanisms governing ciliary trafficking by BBS proteins are not well understood. Here, we show that a novel protein, Leucine-zipper transcription factor-like 1 (LZTFL1), interacts with a BBS protein complex known as the BBSome and regulates ciliary trafficking of this complex. We also show that all BBSome subunits and BBS3 (also known as ARL6) are required for BBSome ciliary entry and that reduction of LZTFL1 restores BBSome trafficking to cilia in BBS3 and BBS5 depleted cells. Finally, we found that BBS proteins and LZTFL1 regulate ciliary trafficking of hedgehog signal transducer, Smoothened. Our findings suggest that LZTFL1 is an important regulator of BBSome ciliary trafficking and hedgehog signaling

TRAF6 Mediates IL-1β/LPS-Induced Suppression of TGF-β Signaling through Its Interaction with the Type III TGF-β Receptor

Transforming growth factor-β1 (TGF-β1) is an important anti-inflammatory cytokine that modulates and resolves inflammatory responses. Recent studies have demonstrated that inflammation enhances neoplastic risk and potentiates tumor progression. In the evolution of cancer, pro-inflammatory cytokines such as IL-1β must overcome the anti-inflammatory effects of TGF-β to boost pro-inflammatory responses in epithelial cells. Here we show that IL-1β or Lipopolysaccharide (LPS) suppresses TGF-β-induced anti-inflammatory signaling in a NF-κB-independent manner. TRAF6, a key molecule in IL-1β signaling, mediates this suppressive effect through interaction with the type III TGF-β receptor (TβRIII), which is TGF-β-dependent and requires type I TGF-β receptor (TβRI) kinase activity. TβRI phosphorylates TβRIII at residue S829, which promotes the TRAF6/TβRIII interaction and consequent sequestration of TβRIII from the TβRII/TβRI complex. Our data indicate that IL-1β enhances the pro-inflammatory response by suppressing TGF-βsignaling through TRAF6-mediated sequestration of TβRIII, which may be an important contributor to the early stages of tumor progression

The Contribution of Occult Precipitation to Nutrient Deposition on the West Coast of South Africa

The Strandveld mediterranean-ecosystem of the west coast of South Africa supports floristically diverse vegetation growing on mostly nutrient-poor aeolian sands and extending from the Atlantic Ocean tens of kilometers inland. The cold Benguela current upwelling interacts with warm onshore southerly winds in summer causing coastal fogs in this region. We hypothesized that fog and other forms of occult precipitation contribute moisture and nutrients to the vegetation. We measured occult precipitation over one year along a transect running inland in the direction of the prevailing wind and compared the nutrient concentrations with those in rainwater. Occult deposition rates of P, N, K, Mg, Ca, Na, Al and Fe all decreased with distance from the ocean. Furthermore, ratios of cations to Na were similar to those of seawater, suggesting a marine origin for these. In contrast, N and P ratios in occult precipitation were higher than in seawater. We speculate that this is due to marine foam contributing to occult precipitation. Nutrient loss in leaf litter from dominant shrub species was measured to indicate nutrient demand. We estimated that occult precipitation could meet the demand of the dominant shrubby species for annual N, P, K and Ca. Of these species, those with small leaves intercepted more moisture and nutrients than those with larger leaves and could take up foliar deposits of glycine, NO3-, NH4 + and Li (as tracer for K) through leaf surfaces. We conclude that occult deposition together with rainfall deposition are potentially important nutrient and moisture sources for the Strandveld vegetation that contribute to this vegetation being floristically distinct from neighbouring nutrient-poor Fynbos vegetation

Omega-3 fatty acids and vitamin D in immobilisation: Part B- modulation of muscle functional, vascular and activation profiles

Abstract Objectives: This study set out to determine whether two potential protein-sparing modulators (eicosapentaenoic acid and vitamin D) would modulate the anticipated muscle functional and related blood vessels function deleterious effects of immobilisation. Design: The study used a randomised, double-blind, placebo-controlled design. Setting: The study took part in a laboratory setting. Participants: Twenty-four male and female healthy participants, aged 23.0±5.8 years. Intervention: The non-dominant arm was immobilised in a sling for a period of nine waking hours a day over two continuous weeks. Participants were randomly assigned to one of three groups: placebo (n=8, Lecithin, 2400 mg daily), omega-3 (-3) fatty acids (n=8, eicosapentaenoic acid (EPA); 1770 mg, and docosahexaenoic acid (DHA); 390 mg DHA, daily) or vitamin D (n=8, 1,000 IU daily). Measurements: Isometric and isokinetic torque, antagonist muscle co-contraction (activation profile), muscle fatigability indices, and arterial resting blood flow were measured before, at the end of the immobilisation period, and two weeks after re-mobilisation. Results: Muscle elbow flexion and extension isometric and isokinetic torque decreased significantly with limb immobilisation in the placebo group (P0.05) towards attenuating the decreases observed in the placebo group. There was no significant change in muscle fatigue parameters or co-contraction values with immobilisation and no effect of supplementation group (P>0.05). Similarly, this immobilisation model had no impact on the assessed blood flow kinetics. All parameters had returned to baseline values at the re-mobilisation phase of the study. Conclusion: Overall, at the current doses, neither -3 nor vitamin D supplementation significantly attenuated declines in torque associated with immobilisation. It would appear that muscle function (described here in Part B) might not be as useful a marker of the effectiveness of a supplement against the impact of immobilisation compared to tissue composition changes (described in Part A)