Surfactant protein-A suppresses eosinophil-mediated killing of Mycoplasma pneumoniae in allergic lungs

Surfactant protein-A (SP-A) has well-established functions in reducing bacterial and viral infections but its role in chronic lung diseases such as asthma is unclear. Mycoplasma pneumoniae (Mp) frequently colonizes the airways of chronic asthmatics and is thought to contribute to exacerbations of asthma. Our lab has previously reported that during Mp infection of non-allergic airways, SP-A aides in maintaining airway homeostasis by inhibiting an overzealous TNF-alpha mediated response and, in allergic mice, SP-A regulates eosinophilic infiltration and inflammation of the airway. In the current study, we used an in vivo model with wild type (WT) and SP-A(-/-) allergic mice challenged with the model antigen ovalbumin (Ova) that were concurrently infected with Mp (Ova+Mp) to test the hypothesis that SP-A ameliorates Mp-induced stimulation of eosinophils. Thus, SP-A could protect allergic airways from injury due to release of eosinophil inflammatory products. SP-A deficient mice exhibit significant increases in inflammatory cells, mucus production and lung damage during concurrent allergic airway disease and infection (Ova+Mp) as compared to the WT mice of the same treatment group. In contrast, SP-A deficient mice have significantly decreased Mp burden compared to WT mice. The eosinophil specific factor, eosinophil peroxidase (EPO), which has been implicated in pathogen killing and also in epithelial dysfunction due to oxidative damage of resident lung proteins, is enhanced in samples from allergic/infected SP-A(-/-) mice as compared to WT mice. In vitro experiments using purified eosinophils and human SP-A suggest that SP-A limits the release of EPO from Mp-stimulated eosinophils thereby reducing their killing capacity. These findings are the first to demonstrate that although SP-A interferes with eosinophil-mediated biologic clearance of Mp by mediating the interaction of Mp with eosinophils, SP-A simultaneously benefits the airway by limiting inflammation and damage.     

Genetic basis of murine antibacterial defense to streptococcal lung infection

To evaluate the effect of genetic background on antibacterial defense to streptococcal infection, eight genetically diverse strains of mice (A/J, DBA/2J, CAST/Ei, FVB/NJ, BALB/cJ, C57BL/6J, 129/SvImJ, and C3H/HeJ) and tlr2-deficient mice (C57BL/6^tlr2−/−) were infected with three doses of Streptococcus zooepidemicus (500, 5,000, or 50,000 colony-forming units) by alveolar challenge. There was a range of susceptibility between the strains at each dose and time point (6, 24, and 96 h). At the lowest dose, the 129/SvImJ and C3H/HeJ strains had significantly higher bacterial counts at all time points after infection, when compared to A/J, DBA/2J, CAST/Ei, FVB/NJ, which were resistant to infection at the low dose of innoculum. At the medium dose, 129/SvImJ and C3H/HeJ had higher bacterial counts, while A/J, DBA/2J, and BALB/cJ showed reduced streptococcal growth. After the highest dose of Streptococcus, there were minimal differences between strains, suggesting the protective impact of modifier genes can be overcome. TLR2-deficient animals contained increased bacterial load with reduced cytokines after 96 h when compared to C57BL/6J controls suggesting a role of innate immunity in late antibacterial defense. Overall, we identify vulnerable (129/SvlmJ and C3H/HeJ) and resistant (A/J, FVB, and DBA) mouse strains to streptococcal lung infection, which demonstrate divergent genetic expression profiles. These results demonstrate that innate differences in pulmonary host defense to S. zooepidemicus are dependent on host genetic factors.     

Endogenous opioid actions and effects of environmental disturbance on parturition and oxytocin secretion in rats

Blood samples were taken from conscious, chronically-catheterized rats during parturition for measurement of oxytocin by specific radioimmunoassay. After the birth of the 3rd pup, rats were allowed to remain in their nesting cage (undisturbed rats) or were transferred for 45 min to a glass bowl (disturbed rats); at the time of transfer, rats were given an i.v. injection of the opioid antagonist naloxone or saline vehicle. Subsequent parturition was prolonged in saline-treated disturbed rats, but not in naloxone-treated disturbed rats. Parturition was significantly hastened in naloxone-treated undisturbed rats. Naloxone injections were followed by a large rise in plasma oxytocin concentrations in disturbed and undisturbed rats. We conclude, from a statistical analysis of the relationship within experimental groups between plasma oxytocin concentration and speed of parturition, that the effects of disturbance and of naloxone upon parturition may be accounted for, at least in part, by their effects upon oxytocin release. However, the effects of disturbance on parturition may not be mediated entirely by activation of opioid pathways. Naloxone did not potentiate oxytocin release in non-pregnant rats, or on Day 1 post partum, but did potentiate oxytocin release on Day 22 of pregnancy even in rats before the onset of parturition. Endogenous opioid pathways regulating oxytocin release therefore appear to be active during late pregnancy and during parturition itself.     

Thomsen-Friedenreich antigen expression in gastric carcinomas is associated with MUC1 mucin VNTR polymorphism

Aberrant glycosylation of mucins is a common phenomenon associated with oncogenic transformation. We investigated the association between expression of the tumor-associated antigens T, Tn, and sialyl-Tn and polymorphism in the length of the MUC1 mucin tandem repeat in a series of gastric carcinomas. We further evaluated the relevance of MUC1 tandem repeat length on the expression of these tumor-associated carbohydrate antigens (TACAs) using a gastric carcinoma cell line model expressing recombinant MUC1 constructs carrying 0, 3, 9, and 42 repeats. Gastric carcinomas showed a high prevalence of Tn and sialyl-Tn antigens, whereas T antigen was less frequently expressed. The expression of T antigen was significantly higher in gastric carcinomas from patients homozygous for MUC1 large tandem repeat alleles. No significant associations were found for Tn and sialyl-Tn antigens. This novel association was reinforced by the gastric carcinoma cell line model experiments, where de novo expression of T antigen was detected in clones transfected with larger VNTR regions. Our results indicate that polymorphism in the MUC1 tandem repeat influences the expression of TACAs in gastric cancer cells and may therefore allow the identification of subgroups of patients that develop more aggressive tumors expressing T antigen.     

Rhizobium lipopolysaccharide modulates infection thread development in white clover root hairs.

The interaction between Rhizobium lipopolysaccharide (LPS) and white clover roots was examined. The Limulus lysate assay indicated that Rhizobium leguminosarum bv. trifolii (hereafter called R. trifolii) released LPS into the external root environment of slide cultures. Immunofluorescence and immunoelectron microscopy showed that purified LPS from R. trifolii 0403 bound rapidly to root hair tips and infiltrated across the root hair wall. Infection thread formation in root hairs was promoted by preinoculation treatment of roots with R. trifolii LPS at a low dose (up to 5 micrograms per plant) but inhibited at a higher dose. This biological activity of LPS was restricted to the region of the root present at the time of exposure to LPS, higher with LPS from cells in the early stationary phase than in the mid-exponential phase, incubation time dependent, incapable of reversing inhibition of infection by NO3- or NH4+, and conserved among serologically distinct LPSs from several wild-type R. trifolii strains (0403, 2S-2, and ANU843). In contrast, infections were not increased by preinoculation treatment of roots with LPSs from R. leguminosarum bv. viciae strain 300, R. meliloti 102F28, or members of the family Enterobacteriaceae. Most infection threads developed successfully in root hairs pretreated with R. trifolii LPS, whereas many infections aborted near their origins and accumulated brown deposits if pretreated with LPS from R. meliloti 102F28. LPS from R. leguminosarum 300 also caused most infection threads to abort. Other specific responses of root hairs to infection-stimulating LPS from R. trifolii included acceleration of cytoplasmic streaming and production of novel proteins. Combined gas chromatography-mass spectroscopy and proton nuclear magnetic resonance analyses indicated that biologically active LPS from R. trifolii 0403 in the early stationary phase had less fucose but more 2-O-methylfucose, quinovosamine, 3,6-dideoxy-3-(methylamino)galactose, and noncarbohydrate substituents (O-methyl, N-methyl, and acetyl groups) on glycosyl components than did inactive LPS in the mid-exponential phase. We conclude that LPS-root hair interactions trigger metabolic events that have a significant impact on successful development of infection threads in this Rhizobium-legume symbiosis.     

Fire severity mediates climate‐driven shifts in understorey community composition of black spruce stands of interior Alaska

Question: How do pre‐fire conditions (community composition and environmental characteristics) and climate‐driven disturbance characteristics (fire severity) affect post‐fire community composition in black spruce stands? Location: Northern boreal forest, interior Alaska. Methods: We compared plant community composition and environmental stand characteristics in 14 black spruce stands before and after multiple, naturally occurring wildfires. We used a combination of vegetation table sorting, univariate (ANOVA, paired t‐tests), and multivariate (detrended correspondence analysis) statistics to determine the impact of fire severity and site moisture on community composition, dominant species and growth forms. Results: Severe wildfires caused a 50% reduction in number of plant species in our study sites. The largest species loss, and therefore the greatest change in species composition, occurred in severely burned sites. This was due mostly to loss of non‐vascular species (mosses and lichens) and evergreen shrubs. New species recruited most abundantly to severely burned sites, contributing to high species turnover on these sites. As well as the strong effect of fire severity, pre‐fire and post‐fire mineral soil pH had an effect on post‐fire vegetation patterns, suggesting a legacy effect of site acidity. In contrast, pre‐fire site moisture, which was a strong determinant of pre‐fire community composition, showed no relationship with post‐fire community composition. Site moisture was altered by fire, due to changes in permafrost, and therefore post‐fire site moisture overrode pre‐fire site moisture as a strong correlate. Conclusions: In the rapidly warming climate of interior Alaska, changes in fire severity had more effect on post‐fire community composition than did environmental factors (moisture and pH) that govern landscape patterns of unburned vegetation. This suggests that climate change effects on future community composition of black spruce forests may be mediated more strongly by fire severity than by current landscape patterns. Hence, models that represent the effects of climate change on boreal forests could improve their accuracy by including dynamic responses to fire disturbance.     

Economic impact of surgical intervention in the treatment of benign prostatic hyperplasia

The economic burden of benign prostatic hyperplasia (BPH) on our health care system is significant and likely to continue to grow given the burgeoning elderly population. Coincident with the rising number of annual physician office visits and expenditures for BPH has been a dramatic shift in the disease's management, from surgical to medical care. However, long-term cost data call into question the appropriateness of medical therapy as the initial treatment approach for all men with BPH, particularly those with moderate to severe symptoms. Although there has been a paradigm shift away from traditional BPH surgery, there has been renewed interest in the treatment of BPH with novel surgical techniques and minimally invasive surgeries. The economics of surgical interventions for BPH are discussed.