Capillary Ultrastructure and the Blood-Brain Barrier in Human Malignant Brain Tumors

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Figures

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    Normal cerebral capillary. Arrows point to endothelial cell junctions. (See text for explanation of callout letters in this and subsequent illustrations.) Lead nitrate, × 12,300.

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    Lanthanum (arrows) can be traced from the area of the basement membrane at the lower left between capillary endothelial cells into the lumen of the capillary. Unstained, × 19,700.

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    Tumor capillary. The entire capillary is similar to the normal one shown in Fig. 1 except for the irregularity and varicosities of the basement membrane and the abnormal cells surrounding the capillary. (A = clear cell process, presumably astrocytic.) Lead nitrate, × 12,300. Inset: High magnification view of endothelial cell junction. Single arrows point to open six-layered portion of the junction. Double arrows denote pentalaminar closed portion of junction. (E = endothelial cell cytoplasm.) Lead nitrate, × 120,000.

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    Tumor capillary. This capillary bears little resemblance to the normal. Endothelial cells are markedly abnormal with hyperchromatic nuclei and bizarre shapes. No basement membrane can be identified through most of the circumference of the vessel. There is a markedly abnormal extracellular space filled with collagen. Lead nitrate, × 5700.

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    Tumor capillary. Arrow denotes attenuated layer of tumor cell cytoplasm abutting basement membrane. This capillary still bears a resemblance to the normal. There is increased vesicular formation in the endothelial cells. The basement membrane is markedly irregular and the outer lamina is difficult to identify in many places. Obviously abnormal cells surround the capillary, and there is a great increase in the extracellular space. Lead nitrate, × 5800.

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    High magnification view of capillary wall. Arrows denote villous processes with vesicular formation. The endothelium pictured here is markedly abnormal with increase in vesicular formation, long luminal processes, and junctions that are apparently open except for fusions near the capillary lumen. Differentiation of basement membrane from extracellular space is quite difficult. Lead nitrate, × 16,500.

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    Endothelial cell hyperplasia in tumor capillary. Arrow denotes abnormal endothelial cell junction. The degree of endothelial cell hyperplasia in this instance has almost occluded the lumen of the vessel. Lead nitrate, × 15,350.

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    Left: Detail of capillary wall. Arrows denote remnant of basement membrane. The endothelial cell cytoplasm in several places is represented by an extremely thin layer which in many areas appears to be no more than two fused plasma membranes. Lead nitrate, × 24,000. Right: Capillary endothelium. The markedly abnormal endothelial cell cytoplasm is discontinuous with a defect apparent at the bottom of the picture. The basement membrane and extracellular space are difficult to differentiate. Lead nitrate, × 23,600.

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    Left: Closed endothelial cell junction in tumor capillary. Arrows denote regions of membrane fusion. Lead nitrate, × 89,400. Right: Tumor endothelial cell junctions. Arrow denotes luminal portion of an endothelial cell junction which is extremely tortuous and widely dilated except in its luminal portion. Lead nitrate, × 11,800.

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    Left: Tumor capillary endothelial cell junction. The lower area denotes an area of apparent fusion in the luminal extremity of the junction while the upper area demonstrates the widely dilated abnormal junction between these capillary endothelial cells. Lead nitrate, × 32,000. Right: Tumor capillary endothelial cell junction. Arrows denote an endothelial cell junction which appear normal at low magnifications. At this high magnification the junction seems to be patent and no membrane fusions closing the junction have occurred. Lead nitrate, × 36,200.

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    Left: Abnormal capillary endothelial cell junction. Arrows denote a tortuous convoluted junction in which membrane thickenings have completely obliterated the fine structure. Lead nitrate, × 28,400. Right: Abnormal endothelial cell junction. Arrows denote a greatly elongated junction which stretches over half the length of the capillary. Lead nitrate, × 14,200.

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    High magnification views of endothelial cell junctions. Arrows denote widely patent junctions between endothelial cells with no evidence of membrane fusion. Lead nitrate, × 120,000.

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    Tumor capillary. The basement membrane is markedly abnormal on showing great dilatations at upper right and lower left (arrows). There is also a loss of electron homogeneity. Lead nitrate, × 14,200.

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    Abnormal basement membrane. Left: The basement membrane is reduplicated, varies in size, and is of irregular electron density. Lead nitrate, ×23,600. Right: The basement membrane is reduplicated and a portion of it contains collagen. Lead nitrate, ×27,200.

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    Abnormal basement membrane. The basement membrane (arrows) in this capillary is represented by little more than an area of increased density immediately adjacent to the endothelial cytoplasm. The extracellular space is filled with collagen. Lead nitrate, × 24,300.

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    Left: Abnormal basement membrane. Arrows denote abnormal junction providing free communication between lumen of capillary on the right and extracellular space on the left. The basement membrane is seen only as an irregular concentration of material of increased electron density immediately adjacent to the capillary endothelial cell. Lead nitrate, × 89,400. Right: Lanthanum in the junction between two endothelial cells is denoted by the arrows. Unstained, × 68,800.

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    Lanthanum (arrows) has filled the basement membrane and extracellular space and darkly outlines all of the endothelial cell junctions from capillary lumen to basement membrane. Unstained, × 17,100.

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