TLR ligands of ryegrass pollen microbial contaminants enhance Th1 and Th2 responses and decrease induction of Foxp3hi regulatory T cells

Microbial contamination of grass pollens could affect sensitization, subsequent allergic response, and efficacy of allergen‐specific immunotherapy. We investigated whether bacterial immunomodulatory substances can direct PBMC responses of allergic and nonatopic subjects against ryegrass pollen (RGP) toward Th1, Th2, or regulatory T (Treg) cells. Aqueous extracts of RGP with high or low LPS were fractionated into large and small molecular weight (MW) components by diafiltration. CFSE‐labeled PBMCs from allergic and nonatopic subjects were stimulated with RGP extracts (RGPEs) and analyzed for cytokine secretion and T‐cell responses. High LPS RGPE increased IFN‐γ⁺ Th1 and IL‐4⁺ Th2 effector cell induction and consistently decreased CD4⁺Foxp3^hi Treg‐cell induction. IL‐10‐producing T‐cell frequency was unaltered, but IL‐10 secretion was increased by high LPS RGPE. RGPE‐stimulation of TLR‐transfected cell lines revealed that high LPS pollen also contained a TLR2‐ligand, and both batches a TLR9‐ligand. Beta‐1,3‐glucans were detected in large and small MW fractions and were also T‐cell stimulatory. In conclusion, coexposure to allergen and proinflammatory microbial stimuli does not convert an established Th2‐ into a Th1‐response. Instead, proinflammatory responses are exacerbated and Foxp3^hi Treg‐cell induction is decreased. These findings show that adjuvants for specific immunotherapy should enhance Treg cells rather than target immune deviation from Th2 to Th1.     

Familial Reactive Perforating Collagenosis: A Case Report

Reactive perforating collagenosis is characterised by trans-epidermal elimination of collagen and is hypothesized to be both autosomally dominant and recessive. We report a family in which two brothers and a sister had lesions of reactive perforating collagenosis.     

Comparison of breast- and formula-fed normal newborns in time to first stool and urine.

BACKGROUND: Although the time to an infant's first stool is used as a marker for a normal GI tract, there have been no studies to date which have evaluated the contribution of the first 24 hours' feeding type to time to first meconium stool, directly comparing breast feeding vs formula feeding. OBJECTIVE: To compare breast- and formula-fed healthy infants > or =34 weeks gestation in time to first stool and urine. STUDY DESIGN: A chart review of 1000 consecutive infants > or =34 weeks of gestational age admitted to the normal newborn nursery of Children's Hospital of Buffalo from June to October 2000. Infants (n=979) were grouped based on feeding type in the first 24 hours: breast-fed (n=211), formula-fed (n=540), and mixed feeding (n=228); n=21 excluded for Neonatal Intensive Care Unit admission. We initially compared the time to first stool and urine between the breast- and formula-fed groups and then examined multiple maternal and infant demographic and clinical factors for their effect on time to first stool using univariate and multivariate analyses. RESULTS: Breast-fed infants were fed earlier and more frequently than formula-fed but there was no significant difference in time to first stool (7.6 vs 7.9 hours). Breast-fed infants were earlier in time to first urine (p=0.03) (7.3 vs 8.5 hours). In multiple regression analysis, gestational age was the only significant (p=0.000) factor in predicting time to first stool. CONCLUSION: Type of feeding did not predict time to first stool but gestational age was important even in this near-term and term population of infants > or =34 weeks gestation.     

CD4+CD25+ T cells alloactivated ex vivo by IL-2 or IL-4 become potent alloantigen-specific inhibitors of rejection with different phenotypes, suggesting separate pathways of activation by Th1 and Th2 responses

CD4(+)CD25(+)Foxp3(+) T cells are regulatory/suppressor cells (Tregs) that include non-antigen (Ag)-specific as well as Ag-specific Tregs. How non-Ag-specific naive CD4(+)CD25(+) Treg develop into specific Tregs is unknown. Here, we generated adaptive Tregs by culture of naive CD4(+)CD25(+)Foxp3(+) T cells with allo-Ag and either interleukin-2 (IL-2) or IL-4. Within days, IL-2 enhanced interferon-gamma receptor (Ifngammar) and Il-5 mRNA and IL-4 induced a reciprocal profile with de novo IL-5Ralpha and increased IFN-gamma mRNA expression. Both IL-2- and IL-4-alloactivated CD4(+)CD25(+) Tregs within 3 to 4 days of culture had enhanced capacity to induce tolerance to specific donor but not to third-party cardiac allografts. These hosts became tolerant as allografts functioned more than 250 days, with a physiologic ratio of less than 10% CD4(+)CD25(+)Foxp3(+) T cells in the CD4(+) population. CD4(+)CD25(+) T cells from tolerant hosts given IL-2-cultured cells had increased Il-5 and Ifngammar mRNA. Those from hosts given IL-4-cultured cells had enhanced IL-5Ralpha mRNA expression and IL-5 enhanced their proliferation to donor but not third-party allo-Ag. Thus, IL-2 and IL-4 activated allo-Ag-specific Tregs with distinct phenotypes that were retained in vivo. These findings suggested that T-helper 1 (Th1) and Th2 responses activate 2 pathways of adaptive Ag-specific Tregs that mediate tolerance. We propose they be known as T-suppressor 1 (Ts1) and Ts2 cells.     

The effect of bedside ultrasound on diagnosis and management of soft tissue infections in a pediatric ED

Background

Presentation of skin and soft tissue infections (SSTIs) to the pediatric emergency department (PED) has increased. Physical examination alone can be inadequate in differentiating cellulitis from an abscess. The purposes of this study were to determine the effect of bedside ultrasound (US) in improving diagnostic accuracy for SSTIs in the PED and to evaluate its effect on the management of patients with SSTIs.

Methods

We conducted a prospective study of a convenience sample of children who presented to an inner-city PED with signs and symptoms of SSTI. The treating physician's pretest opinions regarding the need for incision and drainage and procedural sedation were collected. A bedside US was performed by trained PED physicians to evaluate for cellulitis vs abscess. The treating physician was made aware of the US findings, and the effect on management was recorded.

Results

Sixty-five patients were enrolled, of whom 47 had US-proven abscess and 18 had cellulitis. The sensitivity of US for detection of abscess was 97.5% (95% confidence interval [CI], 90.1%-99.5%), and the specificity was 69.2% (95% CI, 57.8-72.4%). In comparison, the sensitivity for physical examination alone for detection of abscess was 78.7% (95% CI, 71.4%-84.4%), and the specificity was 66.7% (95% CI, 47.6-81.6%). Ultrasound disagreed with clinical examination and changed management in 9 (13.8%) of 65 patients.

Conclusions

Emergency department bedside US improves accuracy in diagnosis of SSTIs. Bedside US changes management in a small but significant number of patients with SSTIs.     

Capillarity-driven assembly of two-dimensional cellular carbon nanotube foams

Capillary forces arising during the evaporation of liquids from dense carbon nanotube arrays are used to reassemble the nanotubes into two-dimensional contiguous cellular foams. The stable nanotube foams can be elastically deformed, transferred to other substrates, or floated out to produce free-standing macroscopic fabrics. The lightweight cellular foams made of condensed nanotubes could have applications as shock-absorbent structural reinforcements and elastic membranes. The ability to control the length scale, orientation, and shape of the cellular structures and the simplicity of the assembly process make this a particularly attractive system for studying pattern formation in ordered media.