Radiation-induced loss of endothelial alkaline phosphatase activity and development of myocardial degeneration. An ultrastructural study.

BACKGROUND: There is general agreement that radiation effects on capillary endothelial cells are a leading event in the pathogenesis of late effects of radiation in normal tissues. The mechanism of microvascular involvement however is unclear. In the myocardium, there is not only a decrease in capillary number, but a focal loss of endothelial alkaline phosphatase. The present study addresses the question of whether radiation-induced alkaline phosphatase loss is due to cell death or to modification of cell function and ultrastructure. EXPERIMENTAL DESIGN: The time course of ultrastructural changes underlying endothelial alkaline phosphatase loss and development of myocardial degeneration was studied in two strains of rat, that differ in latent time of clinical radiation-induced cardiomyopathy. RESULTS: In both strains of rat, development of ultrastructural damage in cardiomyocytes was preceded by a focal loss of endothelial alkaline phosphatase reactivity. The absence of enzyme reaction product was neither due to endothelial cell loss, nor to a depletion in enzyme-bearing cytotoxic vesicles. The endothelial cell/pericyte relationship was also unchanged. Within enzyme-negative areas, there was an increased number of enlarged endothelial cells and of lymphocyte adherence to endothelial cells, which was then followed by endothelial cell rupture and extravasation of blood cells. In Wistar rats, enzyme loss started at 25 days after 20 Gy and reached its maximum extent by 90 days. In Sprague-Dawley rats, which show a significantly higher pre-irradiation enzyme reactivity, the onset of alkaline phosphatase loss and associated alterations was delayed by about 30 days and was significantly less extensive. CONCLUSIONS: Radiation-induced endothelial alkaline phosphatase loss is unrelated to cell death in mitosis, but nonetheless it is relevant for the development of ultimate clinical heart failure.

Cellular localization of endothelial alkaline phosphatase reaction product and enzyme protein in the myocardium.

Myocardial capillary endothelial cells, arteriolar endothelial cells, and the arterial adventitia show positive alkaline phosphatase (AP) enzyme reaction and immunoreactivity in both rat and human hearts. In guinea pigs, however, capillary endothelial staining is discontinuous and arterial adventitia is negative. The ultrastructural correlate of discontinuous capillary staining is a pronounced labeling of pericytes in guinea pig heart and relatively weak endothelial staining. In rat and human heart, enzyme reaction products are localized mainly on plasma membranes and cytotic vesicles of endothelial cells. Comparison of two strains of rat reveals a more dense deposition of enzyme reaction product along the luminal and particularly along the abluminal plasma membrane of Sprague-Dawley rats than of Wistar rats. Quantitative analysis of immunogold labeled anti-AP antibody density confirms the pronounced polarity of capillary endothelial cell labeling in Sprague-Dawley rats. More than 80% of total endothelial AP protein in Sprague-Dawley rats is localized over the abluminal plasma membrane and basal lamina, as compared with less than 30% in Wistar rats. Moreover, the total endothelial cell labeling is almost sixfold higher in Sprague-Dawley than in Wistar rats. Total endothelial labeling and proportion of labeling on the abluminal endothelial plasma membrane in human hearts is intermediate between the two strains of rat. The strain and species differences in enzyme distribution could provide important information concerning enzyme function.

[Two malignant uterine tumors of embryonic tissue residues. (Carcinoma of Gartner's ducts, Mullerian mixed tumor)]. / Zwei bösartige Tumoren des Uterus aus embryonalen Gewebsresten. (Gartnergang-Karzinom, Müllerscher Mischtumor)

Report about a Gartnergang-carcinoma of the cervix uteri of a 24 years old woman. The cytological findings as well as the typical histological characteristics are represented. Persisting particles of the Gartnergang have been proved at the right lateral wall of the cervix uteri and in the lower parts of the corpus uteri. Report about a woman of 62 years. A Mullerian mixed tumour of the corpus uteri with myxoedematous parts has been diagnosed. It must be pointed out, that previous radiotherapy of the true pelvis may possible incluence the development of a Mullerian mixed tumour.