57 research outputs found
Products of cells from gliomas: IX. Evidence that two fundamentally different mechanisms change extracellular matrix expression by gliomas
Four human astrocytic gliomas of high grade of malignancy were each evaluated in tissue and in vitro for percentages of cells expressing glial fibrillary acidic protein (GFAP), collagen type IV, laminin and fibronectin assessed by immunofluorescence with counterstaining of nuclear DNA. Percentages of cells with reticulin and cells binding fluorescein-labeled Ulex europaeus agglutinin were also assessed. In tissue, each extracellular matrix (ECM) component was associated with cells in the walls of abnormal proliferations of glioma vessels, and all four tumors had the same staining pattern. Two strikingly different patterns of conversion of gene product expression emerged during in vitro cultivation. (1). In the most common pattern, percentages of all six markers consistently shifted toward the exact phenotype of mesenchymal cells in abnormal vascular proliferations: increased reticulin, collagen type IV, laminin and fibronectin; markedly decreased glial marker GFAP and absent endothelial marker Ulex europaeus agglutinin. The simplest explanation of this constellation of changes coordinated toward expression of vascular ECM markers is that primary glioma cell cultures are overgrown by mesenchymal cells from the abnormal vascular proliferations of the original glioma. These cell cultures were tested for in situ hybridization (ISH) signals of chromosomes 7 and 10. Cells from one glioma had diploid signals. Cells from the other glioma had aneuploid signals indicating they were neoplastic; however, their signals reflected different numerical chromosomal aberrations than those common to neoplastic glia. (2). The second pattern was different. Cells with ISH chromosomal signals of neoplastic glia retained GFAP, and gained collagen type IV. Their laminin and fibronectin diminished, but persisted among a lower percentage of cells. Cloning and double immunofluorescence confirmed the presence of individual cells with glial and mesenchymal markers. A cell expressing GFAP in addition to either fibronectin, reticulin or collagen type IV is not a known constituent of glioblastoma tissue. This provides evidence of a second mechanism of conversion of gene expression in gliomas.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/45382/1/11060_2005_Article_BF01052843.pd
Recommended from our members
Mechanism of cerebral blood flow augmentation by hemodilution in rabbits
Hemodilution is known to increase cerebral blood flow, but it is not known whether the increase in flow is a direct result of a decrease in viscosity or whether it may be due to compensatory vasodilatation in response to the decrease in oxygen carrying capacity that results from hemodilution. This study is designed to investigate this question. Changes in regional cerebral blood flow were studied in normal and ischemic brains of 15 and 18 rabbits, respectively. In one group of rabbits graded hemodilution was used to reduce arterial oxygen content progressively in stages; in the second group the arterial oxygen content was reduced in similar stages by progressively larger reductions in the concentration of inspired oxygen (hypoxic hypoxia). In the ischemic animals focal ischemia was produced by embolic occlusion of the right middle cerebral artery. In the normal rabbits, hypoxic hypoxia and hemodilution resulted in similar progressive increases in cerebral blood flow as arterial oxygen content fell. In the ischemic animals, there was a significant fall in cerebral blood flow in the ischemic region in all groups after arterial occlusion. Hemodilution resulted in a progressive increase in cerebral blood flow in both ischemic and nonischemic regions. With hypoxic hypoxia, however, cerebral blood flow in the ischemic region showed no increase or a slight decrease. Even though hypoxic hypoxia results in a marked increase in cerebral blood flow in normal brain, it does not significantly change cerebral blood flow in ischemic brain. In contrast, hemodilution resulting in a comparable degree of hypoxemia is capable of significantly increasing cerebral blood flow in ischemic brain. Therefore, the mechanism of blood flow augmentation by hemodilution in ischemic brain is probably related to a direct hemorheologic effect rather than to the resulting hypoxemia
Recommended from our members
Acute effects of isovolemic hemodilution with crystalloids in a canine model of focal cerebral ischemia
We used 44 splenectomized dogs to study the effects of isovolemic hemodilution with a crystalloid solution. The dogs were randomly divided into a hemodilution and a control group. In each group, 17 dogs were subjected to 6 hours of internal carotid and middle cerebral artery occlusion, and five dogs received sham operations. Isovolemic hemodilution by phlebotomy and Ringer's lactate infusion was performed 30 minutes after arterial occlusion and resulted in an average hematocrit of 32-33%. Hemodilution significantly reduced viscosity, fibrinogen and total protein concentrations, and plasma oncotic pressure. Systemic arterial blood pressure and pulmonary wedge pressure decreased slightly with hemodilution, but central venous pressure and pulmonary arterial pressure did not change significantly. There was a similar decrease in cardiac index in both hemodiluted and control dogs, which may have been due to the effects of barbiturate anesthesia. Intracranial pressure increased significantly with time in all dogs subjected to arterial occlusion, but this increase was significantly more severe in the hemodiluted dogs. Specific gravity, measured just after the dogs were killed, 6 hours after hemodilution, was significantly lower in the white matter and basal ganglia of the left (ischemic) hemisphere in hemodiluted dogs than in controls. Regional cerebral blood flow decreased significantly in the left hemisphere after arterial occlusion. This decrease was almost completely reversed by hemodilution except in the basal ganglia, where the increase in edema caused by hemodilution was the greatest
Recommended from our members
Surgical excision of cerebral arteriovenous malformations : late results
- …