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Table 1.

Samples.

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Table 2.

Antibodies.

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Fig 1.

Quantitative analysis of staining by Tissue Fax/Quest.

a) Regions of interest (ROI) with cross-sectioned capillaries only, were manually marked and fields of view (FOV) were scanned. Blue = nuclei stained with DAPI, red = capillaries stained with CD31, yellow = ROI, b) DAPI-stained nuclei are counted as reference parameter and represent the whole cell count within the FOV, c) CD31-stained events are counted in corresponding areas.

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Fig 2.

Detection of CD31+ve and Lectin+ve vessels in serial sections.

a) Lectin (yellow), b) serial section (7 μm apart) stained for CD31 (red), c) Matching areas are indicated in green (artificial colours).

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Fig 3.

Immunofluorescence staining of endothelial markers.

Specific expression of endothelial proteins is shown in red (artificial colour) and nuclei counterstaining in blue (DAPI). CD31 a), E-selectin b), thrombomodulin c), ICAM-1 d), VCAM-1 e) and, Thy-1 f) were expressed on capillaries, small vessels (arterioles, venules) and endocard. Staining was quantitatively assessed only on capillaries, except for VCAM, which was evaluated on the endocard only.

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Fig 4.

Dose-specific effects on tissue markers.

Quantification of immunofluorescence stainings is presented in panel a) for CD31, thrombomodulin, E-selectin; b) ICAM-1, Thy-1, CD45; c) for VCAM, and d) for collagen IV. The number of specifically stained cells per 1000 nuclei around the left ventricle of the heart was normalized on 0 Gy values (= 1). Only for VCAM-1 c), relative values of mean fluorescence intensity (mFI) from endocard stainings are presented. Except for collagen IV d), where age-specific data are shown, data are given as mean of all subgroups (HDR and LDR, at 5 and 8 months, corresponding to 3 and 6 months after irradiation, base and apex) ± SEM, n = 16. Asterisks indicate p-values ≤ 0.05: *, p ≤ 0.01: **, p ≤ 0.001: ***.

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Fig 5.

Histological findings.

Upper row: one animal of the 5-month group (0.5 Gy, LDR) showed disseminated collageneous stripes (*) after sirius red staining a), corresponding accumulations of b) CD45+ve and c) collagen IV+ve cells. Lower row: in four animals of the 8-month group (2 Gy, LDR) similar findings were found: broad collagenous scars d) going along with CD45+ve e) and collagen IV+ve f) immunoreactivity.

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Fig 6.

Dose-dependent effects on plasma markers.

Concentrations of plasma markers were measured 3 (a, c) and 6 (b, d) months after irradiation at the indicated doses at low dose rate (LDR, a,b) and high dose rate (HDR, c,d). Values are presented as mean ± SEM, relative to sham-irradiated control (0 Gy = 1). Missing bars in Fig. 6C are due to analytical failure. Asterisks indicate p-values ≤ 0.05: *, p ≤ 0.01: **, p ≤ 0.001: *** compared to control.

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Fig 7.

Age-specific effects on tissue markers in nonirradiated mice.

The expression of a) CD31, E-selectin, thrombomodulin, ICAM-1, VCAM-1, Thy-1 and of b) CD45 and collagen IV+ve cells is presented in sham-irradiated 0 Gy control mice at 2, 5, and 8 months of age. The relative number of specifically stained cells per 1000 nuclei around the left ventricle of the heart is given (mice at 2 months = 1, mean ± SEM, n = 8). Asterisks indicate p-values ≤ 0.05: *, p ≤ 0.01: **, p ≤ 0.001: *** compared to the 2-month group.

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