Proportion of tumor cells immunolabeled for cyclin D1.

<p>The percentage of tumor cells showing cyclin D1 immunolabeling is indicated in normal thyroid tissue and each case of the various types of papillary thyroid carcinomas: encapsulated and unencapsulated follicular variant of papillary thyroid carcinoma (FVPTC), well differentiated tumor of unknown malignant potential (WDT-UMP), papillary microcarcinoma (PMC) and metastatic papillary thyroid carcinoma (metastatic PTC). Bars indicate the medians. *, p<0.05. The large asterisk above normal thyroid tissue indicates significant difference between the normal tissue and any other variant of PTC.</p

Proportion of tumor cells immunolabeled for phosphorylated histone H3.

<p>The percentage of tumor cells showing phosphorylated histone H3 immunolabeling is indicated in normal thyroid tissue and each case of the various types of papillary thyroid carcinomas: encapsulated and unencapsulated follicular variant of papillary thyroid carcinoma (FVPTC), well differentiated tumor of unknown malignant potential (WDT-UMP), papillary microcarcinoma (PMC) and metastatic papillary thyroid carcinoma (metastatic PTC). Bars indicate the medians. *, p<0.05. The large asterisk above normal thyroid tissue indicates significant difference between the normal tissue and any other variant of PTC.</p

Immunolabeling of proliferative markers.

<p>Representative microphotographs of phosphorylated histone H3 (pHH3; 1) and cyclin D1 immunolabeling (2) in normal thyroid tissue (a) and the various types of papillary thyroid carcinomas: encapsulated (b) and unencapsulated (c) follicular variant of papillary thyroid carcinoma (FVPTC), well differentiated tumor of unknown malignant potential (WDT-UMP; d), papillary microcarcinoma (PMC; e) and metastatic papillary thyroid carcinoma (f). Bars correspond to 50 μm.</p

Proportion of tumor cells immunolabeled for bcl-2.

<p>The percentage of tumor cells showing bcl-2 immunolabeling is indicated in normal thyroid tissue and each case of the various types of papillary thyroid carcinomas: encapsulated and unencapsulated follicular variant of papillary thyroid carcinoma (FVPTC), well differentiated tumor of unknown malignant potential (WDT-UMP), papillary microcarcinoma (PMC) and metastatic papillary thyroid carcinoma (metastatic PTC). Bars indicate the medians. *, p<0.05.</p

Proportion of tumor cells immunolabeled for cleaved caspase-3.

<p>The percentage of tumor cells showing cleaved caspase-3 immunolabeling is indicated in normal thyroid tissue and each case of the various types of papillary thyroid carcinomas: encapsulated and unencapsulated follicular variant of papillary thyroid carcinoma (FVPTC), well differentiated tumor of unknown malignant potential (WDT-UMP), papillary microcarcinoma (PMC) and metastatic papillary thyroid carcinoma (metastatic PTC). Bars indicate the medians. *, p<0.05. The large asterisk above normal thyroid tissue indicates significant difference between the normal tissue and any other variant of PTC.</p

Representative tracings of transrectal potential difference (PD) measurements in baseline conditions in a wild-type mouse and a F508del homozygous mouse.

<p>Tracings show sequential response of the rectal mucosa to perfusion successively with Ringer solution, Ringer solution containing barium and amiloride (Amil), chloride-free solution containing barium and amiloride (0 Cl⁻), and chloride-free solution with barium, amiloride and forskolin. Arrows indicate time of solution changes.</p

Influence of treatment with a single intraperitoneal dose of 0.14/kg vardenafil (vard) or saline on sodium and chloride transport in wild-type (WT), heterozygous (HTZ) and homozygous (CF) mice for the F508del mutation.

<p>Sodium transport evaluated by response to amiloride. Chloride transport evaluated by the cumulative changes in transrectal PD after perfusion with chloride-free solution in the presence of barium, amiloride plus forskolin. Data are shown as means (± SEM) for 5–11 animals per group. P values denote levels of significance of between-group comparisons for the same component of the chloride transport.</p

Influence of treatment with a single intraperitoneal dose of 0.14/kg vardenafil (vard) on the separate components of chloride transport in wild-type mice (WT), in mice heterozygous (HTZ) and homozygous (CF) for the F508del mutation.

<p>Responses of the rectal mucosa to perfusion with chloride-free solution containing barium and amiloride and responses of the rectal mucosa to the further addition of forskolin are shown as means (± SEM) for 5–11 animals per group. P values denote levels of significance of between-group comparisons for the same component of the chloride transport.</p

Immunohistochemical localization studies showing absence of labelling of endogenously expressed CFTR in distal colon tissue from a Cftr knockout mouse (A) and a wild-type mouse (B) in the absence of primary anti-CFTR antibody (w/o Ab).

<p>Immunolabelling performed 1 hour after a single intraperitoneal injection of saline (C,D) or 0.14 mg/kg vardenafil (E,F) in crypt colonocytes from a wild-type mouse (C,E) or a F508del-CF homozygous mouse (D,F). Vardenafil treatment (E,F) increased CFTR (green) labelling at the apical membrane compartment. Nuclei (blue labelling) stained by DAPI. Morphometric analysis of crypt cells with measure of the apical and subapical (corresponding to the rest of the cell height) compartments (G). Mean values and upper/lower 95% confidence intervals (±2SD) of scans of the intensity of the CFTR fluorescence signal along a line drawn through the apical to the basal cell borders obtained from 136 crypt colonocytes from saline-treated wild-type mice; the vertical line marks the apical compartment corresponding to the upper 10% of the height of the cell; total area under the curve = 1285 µm.intensity unit; area under the curve of the apical region = 219.6 µm.intensity unit; peak intensity = 172.8 units; distance from apical membrane to peak intensity = 0.555 µm (H). Normalized ratio of apical/subapical fluorescence CFTR signal (I) and total cell labelling (J) in saline-treated and vardenafil-treated mice.</p

Maximal transrectal PD values (PDmax), response to amiloride and chloride transport (SumCl) in saline-treated wild-type (WT), heterozygous (HTZ) and homozygous (CF) mice for F508del mutation.

<p>Chloride transport was evaluated by the cumulative changes in transrectal PD after perfusion with chloride-free solution in the presence of barium, amiloride plus forskolin. Data are presented as means (±SEM) for 11, 5 and 5 animals in the wild-type and in the F508del heterozygous and homozygous groups respectively. P values denote levels of significance of between-group comparisons for the same transrectal PD parameter.</p