Mice that lack the angiogenesis inhibitor, thrombospondin 2, mount an altered foreign body reaction characterized by increased vascularity.
Disruption of the thrombospondin 2 gene (Thbs2) in mice results in a complex phenotype characterized chiefly by abnormalities in fibroblasts, connective tissues, and blood vessels. Consideration of this phenotype suggested to us that the foreign body reaction (FBR) might be altered in thrombospondin 2 (TSP2)-null mice. To investigate the participation of TSP2 in the FBR, polydimethylsiloxane (PDMS) and oxidized PDMS (ox-PDMS) disks were implanted in TSP2-null and control mice. Growth of TSP2-null and control skin fibroblasts in vitro also was evaluated on both types of disks. Normal fibroblasts grew as a monolayer on both surfaces, but attachment of the cells to ox-PDMS was weak and sensitive to movement. TSP2-null fibroblasts grew as aggregates on both surfaces, and their attachment was further compromised on ox-PDMS. After a 4-week implantation period, both types of PDMS elicited a similar FBR with a collagenous capsule in both TSP2-null and control mice. However, strikingly, the collagenous capsule that formed in TSP2-null mice was highly vascularized and thicker than that formed in normal mice. In addition, abnormally shaped collagen fibers were observed in capsules from mutant mice. These observations indicate that the presence or absence of an extracellular matrix component, TSP2, can influence the nature of the FBR, in particular its vascularity. The expression of TSP2 therefore could represent a molecular target for local inhibitory measures when vascularization of the tissue surrounding an implanted device is desired. (+info)
Disruption of filamentous actin inhibits human macrophage fusion.
The foreign body reaction to implanted biomaterials, characterized by the presence of macrophages and foreign body giant cells (FBGC), can result in structural and functional failure of the implant. Recently, we have shown that interleukin-4 and interleukin-13 can independently induce human macrophage fusion to form FBGC via a macrophage mannose receptor (MR) -mediated pathway. The MR is believed to mediate both endocytosis of glycoproteins and phagocytosis of microorganisms, which bear terminal mannose, fucose, N-acetylglucosamine, or glucose residues. Polarization of microfilaments to closely apposed macrophage membranes as observed with fluorescence confocal microscopy led us to ask whether MR-mediated fusion occurred via a filamentous actin-dependent pathway. Cytochalasins B and D and latrunculin-A, agents that disrupt microfilaments, inhibited macrophage fusion in a concentration-dependent manner. The concentrations of cytochalasins D and B that inhibited fusion did not significantly decrease macrophage adhesion, spreading, or motility but did inhibit internalization of Candida albicans during interleukin-13-enhanced, MR-mediated phagocytosis. Very low concentrations of cytochalasin B (< 2 microM) induced a slight enhancement of macrophage fusion. Taken together, the results of this study suggest that cytokine-induced, MR-mediated macrophage fusion requires an intact F-actin cytoskeleton and that the mechanism of fusion is similar to phagocytosis.--DeFife, K. M., Jenney, C. R., Colton, E., Anderson, J. M. Disruption of filamentous actin inhibits human macrophage fusion. (+info)
Characterization of the importance of polysaccharide intercellular adhesin/hemagglutinin of Staphylococcus epidermidis in the pathogenesis of biomaterial-based infection in a mouse foreign body infection model.
The production of biofilm is thought to be crucial in the pathogenesis of prosthetic-device infections caused by Staphylococcus epidermidis. An experimental animal model was used to assess the importance of biofilm production, which is mediated by polysaccharide intercellular adhesin/hemagglutinin (PIA/HA), in the pathogenesis of a biomaterial-based infection. Mice were inoculated along the length of a subcutaneously implanted intravenous catheter with either wild-type S. epidermidis 1457 or its isogenic PIA/HA-negative mutant. The wild-type strain was significantly more likely to cause a subcutaneous abscess than the mutant strain (P < 0.01) and was significantly less likely to be eradicated from the inoculation site by host defense (P < 0.05). In addition, the wild-type strain was found to adhere to the implanted catheters more abundantly than the PIA/HA-negative mutant (P < 0.05). The reliability of the adherence assay was assessed by scanning electron microscopy. To exclude contamination or spontaneous infection, bacterial strains recovered from the experimental animals were compared to inoculation strains by analysis of restriction fragment length polymorphism patterns by pulsed-field gel electrophoresis. In vitro binding of the wild-type strain and its isogenic mutant to a fibronectin-coated surface was similar. These results confirm the importance of biofilm production, mediated by PIA/HA, in the pathogenesis of S. epidermidis experimental foreign body infection. (+info)
Plastic migration from implanted central venous access devices.
BACKGROUND: This is the first reported study of histologically confirmed migration from intravenous access devices in children. METHODS: The capsules from around intravenous access devices were examined by light microscopy to determine the extent of the foreign body response; energy dispersive x ray analysis was performed to document the elemental content of the foreign material. RESULTS: A fibroconnective tissue capsule was found around all the samples. Elemental silicon was found in six of 13 tissue samples, and a foreign body giant cell reaction was seen in three of these. CONCLUSIONS: The pseudocapsule that surrounds an implanted vascular access device often has residual foreign material, including silicone. (+info)
Symptomatic Rathke's cleft cyst coexisting with central diabetes insipidus and hypophysitis: case report.
We describe a 48-year-old female with acute onset of central diabetes insipidus followed by mild anterior pituitary dysfunction. Magnetic resonance imaging (MRI) revealed enlargement of the hypophysis-infundibulum accompanied by a cystic component. She underwent a transsphenoidal exploration of the sella turcica. Histological examination showed foreign body type xanthogranulomatous inflammation in the neurohypophysis which might have been caused by rupture of a Rathke's cleft cyst. The MRI abnormalities and anterior pituitary dysfunction improved after a short course of corticosteroid administration, but the diabetes insipidus persisted. The histological findings in this case indicated the site of RCC rupture and the direction of the progression of RCC induced neurohypophysitis and adenohypophysitis. (+info)
Efficacy of trisacryl gelatin microspheres versus polyvinyl alcohol particles in the preoperative embolization of meningiomas.
BACKGROUND AND PURPOSE: Trisacryl gelatin microspheres are a new, commercially available nonabsorbable embolic agent. The purpose of this study was to evaluate their efficacy in the preoperative embolization of meningiomas as compared with polyvinyl alcohol (PVA) particles of various sizes. METHODS: In 30 consecutive patients, trisacryl gelatin microspheres (150-300 microm) were used for the preoperative superselective embolization of meningiomas (group 1). Thirty other consecutive patients had embolization with PVA particles of 45 to 150 microm (n = 15, group 2) and of 150 to 250 microm (n = 15, group 3). Extent of devascularization, intraoperative blood loss, blood transfusion, and hemostasis at the time of surgery were recorded for every patient. The inflammatory reaction, the extent of necrotic areas, and the most distal intravascular location of the embolic agent (arterial, arteriolar, precapillary, capillary) were recorded. RESULTS: There was no significant difference in the extent of angiographic devascularization among the groups. Intraoperative blood loss differed significantly between groups 1 and 2 and groups 1 and 3, but not between groups 2 and 3. The trisacryl gelatin microspheres were located more distally in tumor vessels than were the PVA particles of either size. The extent of intratumoral necrosis was not significantly different between the two embolic agents. In all groups there was a mild inflammatory tissue reaction in the vicinity of the embolic agent. CONCLUSION: Trisacryl gelatin microspheres may be effective in the preoperative embolization of meningiomas, producing significantly less blood loss at surgery than seen with PVA particles of either size, possibly because of the significantly more distal vascular penetration of the microspheres. (+info)
MR characteristics of muslin-induced optic neuropathy: report of two cases and review of the literature.
Muslin-induced optic neuropathy is a rarely reported but important cause of delayed visual loss after repair of intracranial aneurysms. Most of the previously reported cases were published before the introduction of MR imaging. We describe the clinical features and MR appearance of two cases of delayed visual loss due to "muslinoma," and compare them with the 21 cases reported in the literature. (+info)
Interferon-gamma protects against biomaterial-associated Staphylococcus epidermidis infection in mice.
Survival of Staphylococcus epidermidis inside macrophages has been recognized as a pivotal process in the pathogenesis of biomaterial-associated infection (BAI). Interferon (IFN)-gamma is a potent activator of macrophages. This study examined whether subcutaneous injections of IFN-gamma can reverse macrophage deactivation induced by implanted biomaterials. Mice received subcutaneous implants combined with an injection of 106 S. epidermidis to induce an experimental BAI. Subsequently, 3 groups of mice received subcutaneous injections of 25,000 IU IFN-gamma 3 times weekly, 10,000 IU IFN-gamma 3 times in 2 weeks, or saline 3 times weekly (saline control), respectively. A fourth group received no injections (control). Segments and tissues of the IFN-gamma-treated mice were significantly less (P<.05) culture positive than those of the control groups. Histologically, the high numbers of intracellularly persisting gram-positive cocci observed in the control mice were absent in the IFN-gamma-treated mice. These data indicate that IFN-gamma protects against experimental BAI. (+info)