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Biomedical subjects

W J Maloney

Publications and source records attributed to W J Maloney.

At least 19 recordsLinked to original sources
PubMed2001

Biochemical analyses of human macrophages activated by polyethylene particles retrieved from interface membranes after failed total hip arthroplasty.

Human monocyte/macrophages (M/M) were exposed to retrieved ultra-high molecular weight polyethylene (UHMWPE) particles isolated after enzymatic digestion of revision total hip arthroplasty interface membrane tissue samples. The cellular response of human M/M to UHMWPE was compared with the response of these cells to latex particles and culture medium alone. We incubated macrophages in good contact with polyethylene particles using an inverted culture system. Chamber slides on which macrophages were attached were filled with polyethylene particle suspension and sealed with plastic sheets. After the slides were inverted, the incubation was completed. Retrieved UHMWPE particulate debris stimulated human M/M to secrete interleukin (IL)-1beta, IL-6, and tumor necrosis factor (TNF)-alpha. Human M/M exposed to retrieved UHMWPE particles secreted significantly more IL-1beta, IL-6, and TNF-alpha compared with M/M exposed to latex particles (P<.05).

Aged↗
PubMed2001

Surgical treatment of pelvic osteolysis.

Sixty-eight well-fixed acetabular cups with osteolysis in the pelvis and polyethylene wear were identified from a series of 124 reoperations for failed cementless sockets. The well-fixed sockets requiring reoperation were subdivided based on whether the liner was exchanged and lytic lesion grafted (Type I case) or the socket was removed and a complete revision was done (Type II case). In 40 patients (Type I cases), the polyethylene liner was exchanged and the osteolytic lesions were debrided. Allograft bone chips were packed into the lytic defect in 29 patients. In the remaining 11 patients, the lesions were debrided but not grafted. At final followup, all of the acetabular components were radiographically stable. No new osteolytic lesions were identified. Approximately 1/3 of the lesions had resolved completely regardless of whether they were grafted. The remaining 2/3 had decreased in size. In 28 patients (Type II cases), the socket was revised. Both strategies were successful in arresting the process of osteolysis during the course of this study (mean, 3.5 years). However, removal of well-fixed sockets was associated with significantly more bone loss.

Adult↗
PubMed2001

Meningeal melanocytoma of the planum sphenoidale. Case report and review of the literature.

Meningeal melanocytoma is a rare benign primary melanotic tumor of the meninges, most commonly found in the spinal canal and the posterior fossa. The authors report the 19th published case of a supratentorial meningeal melanocytoma and the first reported case in which the tumor arose from the planum sphenoidale. The patient's presenting symptoms were characteristic of a large bifrontal lesion and included headaches, personality change, lethargy, and urinary and fecal incontinence. Computerized tomography and magnetic resonance imaging studies revealed an extraaxial lesion arising from the planum sphenoidale. The patient underwent successful gross total removal of the tumor without neurological sequelae. Based on the findings shown in this case report, meningeal melanocytoma should be included in the differential diagnosis of extraaxial lesions arising from the area of the planum sphenoidale.

Female↗
PubMed2000

G-protein activity requirement for polymethylmethacrylate and titanium particle-induced fibroblast interleukin-6 and monocyte chemoattractant protein-1 release in vitro.

Periprosthetic granulomatous membranes consisting of fibroblasts, macrophages, lymphocytes, foreign body giant cells, and abundant particulate debris occur at sites of implant loosening. Previous studies demonstrate that fibroblasts respond to particulate debris through the release of interleukin-6 (IL-6), prostaglandin E(2), and matrix metalloproteinases in vitro. C-C chemokines are observed in granulomatous tissue surrounding loosened prosthetic implants and are released by macrophages and fibroblasts in response to particle challenge in vitro. This study tested the hypothesis that G protein activity is required for fibroblast activation by titanium and polymethylmethacrylate (PMMA) particles, and that inhibition of G protein activity would alter IL-6 and and monocyte chemoattractant protein-1 (MCP-1) release from activated fibroblasts. The specific inhibitor of G protein activity, pertussis toxin, was added to the fibroblasts to examine the effects of G protein activity with respect to the production of IL-6 and MCP-1 by orthopedic biomaterial-challenged fibroblasts in vitro. Interleukin-1beta (IL-1beta), a proven activator of MCP-1 and interleukin-6, was used as a positive control. Exposure of fibroblasts to titanium and polymethylmethacrylate (PMMA) particles resulted in a dose-dependent release of MCP-1 and IL-6. Challenge with PMMA particles at doses of 0.150%, 0.300%, and 0.600% vol/vol increased the release of interleukin-6 by 7-, 19-, and 22-fold, respectively, compared to fibroblasts exposed to serum-free culture medium alone at 24 h. Challenge with PMMA particles at doses of 0.075%, 0.150%, 0.300%, and 0.600% vol/vol increased the release of MCP-1-6 by 2.5-, 3.6-, 4. 3-, and 4.5-fold, respectively, compared to fibroblasts exposed to serum-free culture medium alone. Challenge with titanium particles at concentrations of 0.075%, 0.150%, 0.300%, and 0.600% vol/vol increased the release of interleukin-6 by 2.6-, 6.4-, 9.6-, and 10. 0-fold, respectively, compared to fibroblasts exposed to serum-free culture medium alone at 24 h. Challenge with titanium particles at concentrations of 0.038%, 0.075%, 0.150%, 0.300%, and 0.600% vol/vol increased the release of MCP-1 by 2.9-, 3.1-, 5.8-, 5.4-, and 5. 8-fold, respectively, compared to fibroblasts exposed to serum-free culture medium alone. Pretreatment of fibroblasts with pertussis toxin inhibited the release of interleukin-6 and MCP-1 from PMMA and titanium particle challenged fibroblasts in a dose-dependent manner. PMMA particle induced fibroblast IL-6 release was inhibited by 23.6% and 35.3% with 20- and 200-ng/mL doses of pertussis toxin, respectively. Titanium particle induced fibroblast IL-6 release was inhibited by 48.2% and 56.3% with 20- and 200-ng/mL doses of pertussis toxin, respectively. PMMA particle-induced fibroblast MCP-1 release was inhibited by 36.0%, 50.4%, and 60.1% with 2-, 20- and 200-ng/mL doses of pertussis toxin, respectively. Titanium particle-induced fibroblast MCP-1 release was inhibited by 15.5%, 53.2%, and 64.6% with 2-, 20-, and 200-ng/mL doses of pertussis toxin, respectively. This study suggests that fibroblasts localized in periprosthetic membranes are a source of macrophage chemoattractant factors and proinflammatory mediators that may influence granuloma formation and lead to periprosthetic bone resorption. Furthermore, this study shows that G proteins are involved in particle-induced fibroblast activation, as evidenced by decrease levels of particle induced IL-6 and MCP-1 release following pertussis toxin treatment. (c) 2000 John Wiley & Sons, Inc.

Biocompatible Materials↗
PubMed2000

The bearing surface in total hip arthroplasty: evolution or revolution.

Highly cross-linked polyethylenes represent a new class of polyethylenes that demonstrate dramatic improvements of wear characteristics in laboratory tests. Cross-linked polyethylenes can be manufactured by a number of methods, all of which lead to some changes in the physical properties of the polyethylene. The very limited clinical information about cross-linked polyethylenes available has been favorable. Cross-linked polyethylenes appear to hold promise as an alternative to conventional polyethylene and to hard-on-hard bearing surfaces, but much more clinical information will be required before they can be recommended for routine clinical use.

Biomechanical Phenomena↗
PubMed1999

Interferon-gamma exacerbates polymethylmethacrylate particle-induced interleukin-6 release by human monocyte/macrophages in vitro.

Periprosthetic membranes commonly observed at sites of total joint implant loosening exhibit abundant macrophages and particulate debris. Macrophages phagocytose orthopedic debris and release the pro-inflammatory mediators interleukin-1, interleukin-6, tumor necrosis factor-alpha, and prostaglandin E2. In addition, other immunologic agents, such as interferon-gamma, are present in tissues harvested from the bone-implant interface of failed orthopedic implants. The present study examined the effects of interferon-gamma on polymethylmethacrylate (PMMA) particle-challenged monocyte/macrophages in vitro. The effects of interferon-gamma were determined by measuring interleukin-6 and tumor necrosis factor-alpha release by primary human monocyte/macrophages following exposure to PMMA particles. Exposure of the monocyte/macrophages to PMMA particles resulted in a dose-dependent release of interleukin-6 and tumor necrosis factor-alpha at 48 h. The interleukin-6 release in response to PMMA particle challenge was stimulated by 76% and 127% in the presence of 1.0 and 10.0 ng/mL of interferon-gamma, respectively. Interferon-gamma challenge alone did not alter interleukin-6 release relative to controls. In contrast to interleukin-6, interferon-gamma challenge stimulated tumor necrosis factor-alpha release in a dose-dependent manner. In the presence of particles, addition of 1.0 and 10.0 ng/mL of interferon-gamma resulted in 17% and 171% increases in the levels of tumor necrosis factor-alpha release, respectively, relative to cultures challenged solely with particles. Blocking antibody to IFN-gamma inhibited the effect of IFN-gamma on particle-induced interleukin-6 and tumor necrosis factor-alpha release. The data presented in this study demonstrate that the immunologic modulator interferon-gamma exacerbates monocyte/macrophage release of the pro-inflammatory cytokines interleukin-6 and tumor necrosis factor-alpha in response to PMMA particle challenge in vitro.

Awards and Prizes↗
PubMed1999

Reexpression of type IIA procollagen by adult articular chondrocytes in osteoarthritic cartilage.

OBJECTIVE: To test for the reexpression of the chondroprogenitor splice variant of the gene COL2A1, type IIA procollagen (containing a cysteine-rich NH2 propeptide), in adult articular chondrocytes in osteoarthritic (OA) joint disease. METHODS: In situ hybridization and immunohistochemical localization were performed on normal and OA articular cartilage specimens. The presence of type IIA procollagen messenger RNA (mRNA) expression was confirmed by Northern blot analysis. RESULTS: In normal articular cartilage, no expression of mRNA or presence of type IIA procollagen was found. In OA articular cartilage, focally intense staining for type IIA protein was detected. Consistent with this, chondrocytes, particularly in the middle zones of articular cartilage, expressed type IIA procollagen mRNA. OA repair cartilage typically showed a broad zone of cells expressing type IIA mRNA and protein. CONCLUSION: Type IIA procollagen is reexpressed by adult articular chondrocytes in OA cartilage degeneration, indicating the potential reversion of the cells to a chondroprogenitor cellular phenotype. The absence of type IIA mRNA and protein in normal adult articular cartilage and its onset in the diseased state suggests type IIA procollagen as a marker of OA.

Adult↗
PubMed1999

Reduced bone stress as predicted by composite beam theory correlates with cortical bone loss following cemented total hip arthroplasty.

Clinical and experimental evidence suggest that periprosthetic bone loss following total hip arthroplasty is caused in part by stress-shielding. Changes in bone stress in the proximal femur following implantation can be estimated with use of composite beam theory. We hypothesized that the degree of stress-shielding predicted by beam theory correlates with the magnitude of bone loss following cemented total hip arthroplasty. We analyzed cross sections from the proximal femur of 13 patients who had undergone unilateral cemented total hip arthroplasty. A matching implant was inserted contralaterally, and the cross-sectional properties of the implant and bone and the bone density were determined. Bone loss was calculated on the basis of differences between contralateral (control) and ipsilateral (remodeled) sections and correlated to several beam-theory parameters calculated from the control sections: implant rigidity, bone rigidity, ratio of implant to bone rigidity, and predicted decrease in bone stress. All parameters except implant rigidity were significantly correlated with bone loss (p < 0.05). Parameters that included implant and bone properties were more strongly correlated with bone loss than were those based on bone properties alone. The predicted decrease in bone stress explained 50-60% of the variance in bone loss. The data also indicated that patients were not likely to lose substantial amounts of bone unless the reduction in bone stress exceeded a threshold value. Although limited by a small and heterogeneous sample, these results indicate that beam-theory predictions correlate with the degree of femoral resorption and should be investigated further as a means to identify patients at high risk for bone loss.

Arthroplasty, Replacement, Hip↗
PubMed1999

Interleukin-4 inhibits granulocyte-macrophage colony-stimulating factor, interleukin-6, and tumor necrosis factor-alpha expression by human monocytes in response to polymethylmethacrylate particle challenge in vitro.

The outcome of total joint arthroplasty is determined by biological events at the bone-implant interface. Macrophages phagocytose implant or wear debris at the interface and release proinflammatory mediators such as interleukins 1 and 6, tumor necrosis factor-alpha, and prostaglandin E2. These mediators are thought to contribute to the resorption of periprosthetic bone. Previous studies of tissues harvested from the bone-implant interface of failed orthopaedic implants demonstrated a possible role for two other cytokines, granulocyte-macrophage colony-stimulating factor and interleukin-4. The present study examined the effects of in vitro challenge with polymethylmethacrylate particles on the expression of granulocyte-macrophage colony-stimulating factor by primary human monocytes/macrophages and the role of interleukin-4 in regulating this expression. The polymethylmethacrylate particles caused a dose-dependent release of granulocyte-macrophage colony-stimulating factor at 48 hours. This release was accompanied by increased expression of interleukins 6 and 1beta and tumor necrosis factor-alpha. Release of the lysosomal enzyme hexosaminidase also increased in response to the particles. Interleukin-4 inhibited the expression of granulocyte-macrophage colony-stimulating factor, interleukin-6, and tumor necrosis factor-alpha at 48 hours in a dose-dependent manner. The data presented in this study confirm the hypothesis that interleukin-4 downregulates particle-induced activation of macrophages, as demonstrated by the decreased release of proinflammatory mediators.

Dose-Response Relationship, Drug↗
PubMed1999

Fixation, polyethylene wear, and pelvic osteolysis in primary total hip replacement.

A multicenter retrospective review was performed analyzing 1081 primary total hip replacements in 944 patients using the Harris Galante-I cementless acetabular component with screw fixation. All patients were followed up for a minimum of 5 years with a mean followup of 81 months. Linear polyethylene wear averaged 0.11 mm/year (range, 0-0.86 mm/year). Pelvic osteolysis was seen in 25 patients (2.3%). Migration of the acetabular component was seen in four hips. A subgroup of patients was reanalyzed at a minimum followup of 10 years. The mean linear polyethylene wear rate remained 0.11 mm/year. In this group, only one socket had migrated. There was an association between wear rate and age. On average, younger patients had higher wear rates. The risk for having pelvic osteolysis develop and the need for revision surgery also was age-related. Twenty-two percent of hip replacements (15 hips) in patients younger than 50 years of age at the time of their index operation had pelvic osteolysis develop. In contrast, for patients older than 50 years of age at the time of surgery only 7.8% (eight hips) had osteolysis of the pelvis develop. For patients older than 70 years of age at the time of primary total hip replacement, none had pelvic osteolysis develop.

Adolescent↗
PubMed1999

Induction of macrophage C-C chemokine expression by titanium alloy and bone cement particles.

Particulate wear debris is associated with periprosthetic inflammation and loosening in total joint arthroplasty. We tested the effects of titanium alloy (Ti-alloy) and PMMA particles on monocyte/macrophage expression of the C-C chemokines, monocyte chemoattractant protein-1 (MCP-1), monocyte inflammatory protein-1 alpha (MIP-1alpha), and regulated upon activation normal T expressed and secreted protein (RANTES). Periprosthetic granulomatous tissue was analysed for expression of macrophage chemokines by immunohistochemistry. Chemokine expression in human monocytes/macrophages exposed to Ti-alloy and PMMA particles in vitro was determined by RT-PCR, ELISA and monocyte migration. We observed MCP-1 and MIP-1alpha expression in all tissue samples from failed arthroplasties. Ti-alloy and PMMA particles increased expression of MCP-1 and MIP-1alpha in macrophages in vitro in a dose- and time-dependent manner whereas RANTES was not detected. mRNA signal levels for MCP-1 and MIP-1alpha were also observed in cells after exposure to particles. Monocyte migration was stimulated by culture medium collected from macrophages exposed to Ti-alloy and PMMA particles. Antibodies to MCP-1 and MIP-1alpha inhibited chemotactic activity of the culture medium samples. Release of C-C chemokines by macrophages in response to wear particles may contribute to chronic inflammation at the bone-implant interface in total joint arthroplasty.

Antibodies, Monoclonal↗
PubMed1999

Signaling pathways for tumor necrosis factor-alpha and interleukin-6 expression in human macrophages exposed to titanium-alloy particulate debris in vitro.

BACKGROUND: Loosening of the implant after total joint arthroplasty remains a serious problem. The activation of macrophages by wear debris from implants, mediated by the release of cytokines that elicit bone resorption, may lead to loosening. The purpose of the present study was to elucidate the mechanisms of macrophage activation by titanium particles from the components of implants and to identify the signaling pathways involved in particle-mediated release of cytokines. METHODS: Macrophages were isolated from mononuclear leukocytes obtained from healthy human donors and were exposed to titanium-alloy particles that had been obtained from periprosthetic membranes collected at revision total joint arthroplasties and then enzymatically prepared. The experimental protocols included examination of the effects of the inhibition of phagocytosis and the binding of antibodies to macrophage complement receptors on particle-induced macrophage activation. The release of the proinflammatory cytokines TNF-alpha (tumor necrosis factor-alpha) and IL-6 (interleukin-6) was used to assess macrophage activation. The signaling pathways involved in the induction of cytokine release were analyzed by identification of phosphorylated proteins with use of the Western blot technique and by translocation of the transcription factors nuclear factor-kappa B (NF-kappaB) and nuclear factor-interleukin-6 (NF-IL-6) into the nuclear protein fraction with use of electrophoretic mobility shift assays. The role of serine/threonine and tyrosine kinase pathways in the activation of nuclear factors and the release of cytokines was examined with use of selective pharmacological agents. RESULTS: Exposure of macrophages to titanium-alloy particles in vitro for forty-eight hours resulted in a fortyfold increase in the release of TNF-alpha and a sevenfold increase in the release of IL-6 (p<0.01). Phagocytosis of particles occurred in approximately 73 percent of the macrophages within one hour of exposure. Pretreatment of the macrophages with cytochalasin B reduced phagocytosis by 95 percent but did not reduce the release of TNF-alpha or IL-6. Thus, phagocytosis of particles was not necessary for induction of the release of TNF-alpha or IL-6 in the cultured macrophages. Ligation of the macrophage CD11b/CD18 receptors by integrin-specific antibodies also increased the release of TNF-alpha and IL-6. Antibodies to CD11b/ CD18 receptors (macrophage Mac-1 receptors) reduced phagocytosis of particles by 50 percent (p<0.05). (The CD11b/CD18 macrophage receptor is the macrophage receptor for the complement component CR3bi. The CD11b/CD18 macrophage receptor can also bind to ICAM-1 and ICAM-2. CD is the abbreviation for cluster of differentiation, and ICAM is the abbreviation for intercellular adhesion molecule.) Inhibition of phagocytosis was not accompanied by a decrease in the release of TNF-alpha and IL-6. Blocking RNA synthesis with actinomycin D or preventing protein synthesis with cycloheximide abolished or decreased particle-induced release of TNF-alpha and IL-6 from the macrophages. Macrophage release of TNF-alpha and IL-6 in response to particles coincided with increased tyrosine phosphorylation and mitogen-activated protein kinase activation. Inhibition of tyrosine and serine/threonine kinase activity decreased the particle-induced release of cytokines. Exposure of macrophages to either titanium-alloy particles or to antibodies to the receptor proteins CD11b and CD18 for thirty minutes activated the transcription factors NF-kappaB and NF-IL-6. Inhibition of particle phagocytosis did not block activation of the transcription factors. However, inhibition of tyrosine and serine/threonine kinase activity decreased the activation of NF-kappaB and NF-IL-6. CONCLUSIONS: These data suggest that particle induced macrophage release of TNF-alpha and IL-6 does not require phagocytosis but is dependent on tyrosine and serine/threonine kinase activity culminating in activation of

Alloys↗
PubMed1998

Effects of serum protein opsonization on cytokine release by titanium-alloy particles.

This study tested whether macrophages respond differently to retrieved titanium-alloy particles than they do to machined titanium-alloy particles and assessed whether pretreatment of machined titanium-alloy particles with human serum would influence macrophage activation and cytokine release in vitro. Human monocyte/macrophages were isolated from normal healthy donors and exposed to increasing concentrations of machined and retrieved titanium-alloy particles. The profile of cytokine release was determined by commercially available ELISA kits. Machined titanium-alloy particles were opsonized with human serum and added to macrophage cultures. Serum protein binding was confirmed by SDS-PAGE analysis. The results showed that machined titanium-alloy particles and retrieved titanium-alloy particles stimulate a similar level of cytokine release when tested at comparable concentrations. Opsonization of the machined particles with human serum increased the macrophage release of cytokines in the first 12 h after exposure compared to nonopsonized particles. At 24 h, the opsonized particles stimulated significantly higher levels of cytokine release, but only at the greatest particle concentrations. This study demonstrates that machined titanium alloy induces a metabolic response in macrophages similar to that of titanium-alloy particles retrieved from failed total hip arthroplasty. In addition, these data show that serum protein binding to orthopedic biomaterial debris alters the macrophage reaction to the particles.

Alloys↗