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1.
Fig. 4.

Fig. 4. From: Loss of Cftr function exacerbates the phenotype of Na+ hyperabsorption in murine airways.

Prominent airway epithelial cell necrosis in ΔF508 CF/βENaC-Tg mice. AC: representative photomicrographs of airway epithelia from 5-day-old ΔF508 CF (ΔF; A), βENaC-Tg (βENaC; B), and ΔF508 CF/βENaC-Tg (ΔF/βENaC; C) mice. H&E stain, scale bar = 20 μm. D: morphometric quantification of necrotic cells in 5-day-old mice. *P < 0.05 vs. WT mice, #P < 0.05 vs. βENaC-Tg mice.

Alessandra Livraghi-Butrico, et al. Am J Physiol Lung Cell Mol Physiol. 2013 April 1;304(7):L469-L480.
2.
Fig. 7.

Fig. 7. From: Loss of Cftr function exacerbates the phenotype of Na+ hyperabsorption in murine airways.

Spontaneous bacterial colonization in mice from the ΔF508 CF × βENaC-Tg cross. A: analysis of total colony forming units (CFU) in BAL samples from 5-day-old mice. (Log10+1)-transformed data; n = number of mice/group. *P < 0.05 vs. WT littermates. B: individual CFUs and bacterial species isolated from 5-day-old mice. Each tick on the x-axis represents an individual mouse.

Alessandra Livraghi-Butrico, et al. Am J Physiol Lung Cell Mol Physiol. 2013 April 1;304(7):L469-L480.
3.
Fig. 2.

Fig. 2. From: Loss of Cftr function exacerbates the phenotype of Na+ hyperabsorption in murine airways.

ΔF508 CF/βENaC-Tg mice exhibit increased Na+ absorption and defective Cl secretion. Ion transport properties of freshly excised tracheal tissues of 3-day-old mice (A), 10-day-old mice (B), and adult mice (C) from the ΔF508 CF × βENaC-Tg cross. “Basal” indicates the short-circuit current (Isc) before drug application. The change in Isc (Δ) after sequential drug addition is shown. “Residual” Isc is the Isc remaining after amiloride application. *P < 0.05 vs. WT mice, #P < 0.05 vs. βENaC-Tg mice, ≠P < 0.05 vs. βENaC-Tg mice in B, and P < 0.05 vs. ΔF508 CF (ΔF) and ΔF508 CF/βENaC-Tg (ΔF/βENaC) mice in C.

Alessandra Livraghi-Butrico, et al. Am J Physiol Lung Cell Mol Physiol. 2013 April 1;304(7):L469-L480.
4.
Fig. 1.

Fig. 1. From: Loss of Cftr function exacerbates the phenotype of Na+ hyperabsorption in murine airways.

Gross findings in double-mutant ΔF508 CF/βENaC-Tg mice compared with wild-type (WT), ΔF508 CF (mice carrying the ΔF508 Cftr mutation), and βENaC-Tg (transgenic mice with overexpression of the epithelial Na+ channel β subunit) littermates. A: survival curves for mice from the ΔF508 CF × βENaC-Tg cross indicate reduced survival in ΔF508 CF/βENaC-Tg mice (ΔF/βENaC) compared with ΔF508 CF (ΔF) and βENaC-Tg (βENaC) littermates. *P < 0.05 vs. WT mice, #P < 0.05 vs. βENaC-Tg mice. B: comparison of body weights at 5 days of age shows decreased body weight in ΔF508 CF, βENaC-Tg, and ΔF508 CF/βENaC-Tg mice. *P < 0.05 vs. WT mice, #P < 0.05 vs. βENaC-Tg mice.

Alessandra Livraghi-Butrico, et al. Am J Physiol Lung Cell Mol Physiol. 2013 April 1;304(7):L469-L480.
5.
Fig. 3.

Fig. 3. From: Loss of Cftr function exacerbates the phenotype of Na+ hyperabsorption in murine airways.

ΔF508 CF/βENaC-Tg mice exhibited airway and lung pathology distinct from ΔF508 CF and βENaC-Tg mice. A and B: representative photomicrographs of tracheas from 3-day-old WT (A) and ΔF508 CF/βENaC-Tg (B) mice, illustrating tracheal abnormalities in the latter. Tracheas from ΔF508 CF mice exhibited the same tracheal defect as in B. Scale bar = 100 μm. C: representative photomicrographs of lung histology in 5-day-old WT, ΔF508 CF (ΔF), βENaC-Tg (βENaC), and ΔF508 CF/βENaC-Tg (ΔF/βENaC) mice. Hematoxylin and eosin (H&E) stain, low magnification, scale bar = 200 μm. Rectangles indicate areas shown at higher magnification in the insets, scale bar = 20 μm. Arrows indicate dense neutrophil aggregates, commonly found in ΔF508 CF/βENaC-Tg mice airway lumen. D: comparison of lung volumes at 5 days of age shows equivalent air space enlargement in βENaC-Tg and ΔF508 CF/βENaC-Tg mice. *P < 0.05 vs. WT mice.

Alessandra Livraghi-Butrico, et al. Am J Physiol Lung Cell Mol Physiol. 2013 April 1;304(7):L469-L480.
6.
Fig. 6.

Fig. 6. From: Loss of Cftr function exacerbates the phenotype of Na+ hyperabsorption in murine airways.

Quantification of airway inflammatory infiltrate and inflammatory mediators profile indicate more severe lung pathology in ΔF508 CF/βENaC-Tg mice. A: differential bronchoalveolar lavage (BAL) cell counts in 5-day-old WT, ΔF508 CF (ΔF), βENaC-Tg (βENaC), and ΔF508 CF/βENaC-Tg (ΔF/βENaC) mice. *P < 0.05 vs. WT mice, #P < 0.05 vs. βENaC-Tg mice. B: BAL fluid (BALF) cytokines in 5-day-old mice. Dotted line represents the assay lower detection limit (LOD). *P < 0.05 vs. WT mice, #P < 0.05 vs. βENaC-Tg mice. TNF-α, tumor necrosis factor-α; KC, keratinocyte-derived cytokine; MIP-2, macrophage inflammatory protein; LIX, lipopolysaccharide-induced CXC chemokine; MIP-1α, macrophage inflammatory protein-1; G-CSF, granulocyte colony-stimulating factor; M-CSF, macrophage colony-stimulating factor; IL-6, interleukin-6; MCP-1, monocyte chemoattractant protein-1; IL-1α, interleukin-1α; IL-1β, interleukin-1β; GM-CSF, granulocyte-macrophage colony-stimulating factor. C: differential BAL cell counts in 10-mo-old ΔF508 CF and ΔF508 CF/βENaC-Tg mice. BAL cell counts in 12-mo-old WT and congenic C57BL/6N βENaC-Tg mice from (26) are plotted in the same graph for comparison. *P < 0.05 vs. WT mice, #P < 0.05 vs. βENaC-Tg mice.

Alessandra Livraghi-Butrico, et al. Am J Physiol Lung Cell Mol Physiol. 2013 April 1;304(7):L469-L480.
7.
Fig. 5.

Fig. 5. From: Loss of Cftr function exacerbates the phenotype of Na+ hyperabsorption in murine airways.

Surviving ΔF508 CF/βENaC-Tg mice exhibit severe lung pathology reminiscent of eosinophilic crystalline pneumonia. A and B: representative micrograph of lung histopathology in 10-mo-old ΔF508 CF (A), βENaC-Tg (B), and ΔF508 CF/βENaC-Tg (C) mice. H&E stain, scale bar 100 μm. C: lung pathology in adult ΔF508 CF/βENaC-Tg mice comprised airway mucus obstruction (arrow), bronchial-associated lymphoid tissue (BALT) (arrowhead), and extensive lobar consolidation. D: intraluminal mucus plugs (MP), granulocytes (G), hypertrophic macrophages (M), and eosinophilic crystals (C), scale bar = 10 μm. E and F: dense aggregates of hypertrophic and vacuolated macrophages in the parenchyma and airway lumen, respectively. G: substantial immunoreactivity for YM1/2 in alveolar macrophages (solid arrows) and epithelial cells (dotted arrows). H: immunoreactivity for CCSP in the lumen (solid arrows) and epithelial cells (dotted arrows). ep, Epithelium; aa, airway lumen; ap, alveolar parenchyma. I: BALT, adjacent a small bronchiole filled with hypertrophic macrophages. J and K: Russell bodies, large cytoplasmic inclusions identifiable as eosinophilic if stained with H&E (J) or glycoprotein-rich if stained with Alcian blue-periodic acid Schiff staining (AB-PAS; K).

Alessandra Livraghi-Butrico, et al. Am J Physiol Lung Cell Mol Physiol. 2013 April 1;304(7):L469-L480.

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