Ann M. Dvorak

Defective Associations between Blood Vessels and Brain Parenchyma Lead to Cerebral Hemorrhage in Mice Lacking αv Integrins

ABSTRACT Mouse embryos genetically null for the αv integrin subunit develop intracerebral hemorrhages at midgestation and die shortly after birth. A key question is whether the hemorrhage arises from primary defects in vascular endothelial cells or pericytes or from other causes. We have previously reported normal initiation of cerebral vessels comprising branched tubes of endothelial cells. Here we show that the onset of hemorrhage is not due to defects in pericyte recruitment. Additionally, most αv-null vessels display ultrastructurally normal endothelium-pericyte associations and normal interendothelial cell junctions. Thus, endothelial cells and pericytes appear to establish their normal relationships in cerebral microvessels. However, by both light and electron microscopy, we detected defective associations between cerebral microvessels and the surrounding brain parenchyma, composed of neuroepithelial cells, glia, and neuronal precursors. These data suggest a novel role for αv integrins in the association between cerebral microvessels and central nervous system parenchymal cells.

Fibrin Formation: Implications for Tumor Growth and Metastasis

Whether undertaken by pathologists, immunologist, or biochemists, studies of tumor biology have traditionally concentrated on the malignant cells themselves, their abnormal morphology, their altered metabolism and more recently, their panoply of surface antigens. Yet, tumors are comprised not only of malignant cells but also of stroma. In the case of many solid tumors stroma may actually comprise the bulk of the mass perceived as tumor with the naked eye. In any event, tumors are dependent on stroma for nutrient supply and removal of metabolic wastes. Tumor stroma is not a homogeneous entity but rather consists of several connective tissue elements including collagen of several types, elastin, fibronectin, glycosaminoglycans, interstitial fluid, new blood vessels and, as we shall discuss in this chapter, fibrin.

Purification of Basophilic Leukocytes from Guinea Pig and Human Blood and from Guinea Pig Bone Marrow

Publisher Summary This chapter discusses the purification of basophilic leukocytes from guinea pig and human blood and from guinea pig bone marrow. A complete understanding of basophil function requires the analysis of cloned cell lines together with cells freshly isolated from the blood or bone marrow. The examination of freshly isolated cells represents an important tool for understanding alterations in basophil function that may accompany immune responses or allergic diseases. The extent of the peripheral basophilia is the single most important variable affecting basophil purification. Although all guinea pigs primed with whole sheep blood develop increased circulating basophils, the magnitude of this response varies enormously from < 5- to more than 200-fold. Basophil counts performed on ear capillary blood are often considerably higher than those of arterial or cardiac blood obtained at the same time. Purified basophils may be obtained from both the peripheral blood and bone marrow of the same donor animals that have been stimulated with daily injections of sheep blood.