Biomedical subjects

Mark J Fisher

Publications and source records attributed to Mark J Fisher.

4 recordsLinked to original sources

PubMed2006

Brain endothelial hemostasis regulation by pericytes.

Pericytes are known to regulate brain capillary endothelial functions. The purpose of this study was to define the hemostatic regulatory role of human brain pericytes. We used blood-brain barrier models consisting of human pericytes grown on transwell membrane inserts and cocultured with human brain microvascular endothelial cells (HBEC), or pericytes grown in direct contact with HBEC. When grown in cocultures in which pericytes were physically separated from endothelial cells, pericytes induced significant changes in endothelial tissue plasminogen activator (tPA) messenger ribonucleic acid (mRNA) and protein: tPA mRNA level was decreased in pericyte cocultures (52%+/-25% of monocultures, P < 0.05) and tPA protein level was decreased (66%+/-23% of monocultures, P < 0.05). Pericyte effects on endothelial fibrinolysis were enhanced when the two cell types were cocultured in direct contact, with tPA protein reduced in cocultures compared with monocultures (25%+/-15% of monocultures, P < 0.05). Endotoxin (lipopolysaccharide (LPS)), used as a standardized stimulus to define brain-specific inflammation-induced change, amplified pericyte-induced enhanced release of the tPA inhibitor plasminogen activator inhibitor-1 (PAI-1); the latter was released by endothelial cells first cocultured with pericytes and then incubated with LPS in the absence of pericytes. Pericytes (in contrast to endothelial cells and astrocytes) were found to be the principal in vitro source of the serpin protease nexin-1 (PN-1), known to have primarily antithrombin effects. These in vitro findings suggest that pericytes negatively regulate brain endothelial cell fibrinolysis, while pericyte expression of PN-1 may provide endogenous anticoagulant activity.

Amyloid beta-Protein Precursor↗

PubMed2004

Minimally oxidized low-density lipoprotein regulates hemostasis factors of brain capillary endothelial cells.

Minimally oxidized low-density lipoprotein (MM-LDL) is a potent atherogenic lipoprotein. We analyzed the effects of MM-LDL on brain capillary endothelial expression of plasminogen activator inhibitor-1 (PAI-1), tissue-type plasminogen activator (tPA), and thrombomodulin (TM). Cultured bovine brain capillary endothelial cells (BEC) incubated with MM-LDL (25 microg/ml) for 24 h showed increased PAI-1 mRNA levels by approximately seven-fold, while tPA and TM mRNA levels were reduced by 84% and 75%, respectively. Moreover, PAI-1 protein levels increased two-fold (16.8+/-7.6 vs. 7.6+/-2.1 ng/ml, p<0.05), whereas tPA protein levels decreased by 45% (1.3+/-0.5 ng/ml vs. 2.3+/-0.7 ng/ml, p<0.05), and TM protein level decreased by 40%. Following incubation with MM-LDL, PAI-1 activity was increased 35% (18.4+/-5.0 vs. 24.8+/-5.2 AU/ml, p<0.05), while TM activity was decreased by 30%. MM-LDL therefore has substantial pro-thrombotic effects on brain capillary endothelial cells, reducing both endothelial fibrinolytic capacity (downregulating tPA while upregulating PAI-1) and anticoagulant function (downregulating TM). These results suggest that MM-LDL may contribute to thrombus formation in the brain.

Animals↗

PubMed2003

Astrocyte regulation of human brain capillary endothelial fibrinolysis.

INTRODUCTION: Astrocytes are known to regulate a wide variety of brain endothelial cell functions. Prior work, using a mixed species co-culture system, has shown astrocyte regulation of brain capillary endothelial expression of key hemostasis factors tissue plasminogen activator (tPA) and its inhibitor, plasminogen activator inhibitor-1 (PAI-1). The purpose of this study is to define the fibrinolytic regulatory role of human astrocytes on human brain capillary endothelial cells. MATERIALS AND METHODS: We used a blood-brain barrier model consisting of human astrocytes grown on transwell membrane inserts and co-cultured with human brain capillary endothelial cells. Following 48 h co-culture, we analyzed both endothelial mono-cultures and astrocyte-endothelial co-cultures for expression of tPA and PAI-1 mRNA, protein, and activity. RESULTS AND CONCLUSIONS: There were significant changes for both tPA and PAI-1 mRNA:tPA mRNA levels were decreased in co-cultures (55+/-16% of mono-cultures, p<0.0005) and PAI-1 mRNA levels were increased 144+/-38%, compared to mono-cultures (p<0.005). Co-cultures produced a 54% reduction in tPA protein (12.7+/-3.8 vs. 27.5+/-7.1 ng/ml, p<0.005) and a 24% increase in PAI-1 protein (117.5+/-3.2 vs. 94.9+/-5.9 ng/ml, p<0.0005). TGF-beta neutralizing antibody attenuated the observed changes in both tPA and PAI-1. These data indicate that human astrocytes regulate human brain capillary fibrinolysis in vitro by inhibiting tPA and enhancing PAI-1 expression. This regulation is mediated, in part, by transforming growth factor-beta. Our findings provide further evidence for the role of astrocytes in brain-specific hemostasis regulation.

Astrocytes↗

PubMedDate not supplied

Instructional tools for nursing education: concept maps.

Students must deal with vast amounts of information in multiple formats, yet their ability to organize and link data in a logical way varies widely. Concept mapping offers nurse educators a useful tool to assist nursing students in wading through and critically analyzing this information more effectively. This article explains concept/cognitive mapping as a teaching strategy for several aspects of course work. Types and examples of maps developed by undergraduate and graduate students are used as illustrations and points of discussion. Illustrations are assessed according to type of map, information presented, aspects of the maps that facilitate meaningful learning, and what information is missing. Strategies for remediation to help learners assimilate new information are included. Finally, implementation of mapping in nursing education and ideas for research in concept/cognitive mapping are discussed.

Concept Formation↗