Biomedical subjects

S B Goodman

Publications and source records attributed to S B Goodman.

At least 19 recordsLinked to original sources

PubMed2007

Effects of a p38 MAP kinase inhibitor on bone ingrowth and tissue differentiation in rabbit chambers.

The effects of an oral p38 mitogen-activated protein kinase (MAPK) inhibitor and polyethylene particles separately and together on tissue differentiation in the bone harvest chamber (BHC) in rabbits over a 3-week treatment period were investigated. The harvested tissue was analyzed histomorphometrically for markers of bone formation (percentage of bone area), osteoblasts (alkaline phosphatase staining), and osteoclasts (CD51, the alpha chain of the vitronectin receptor). Polyethylene particles decreased the percentage of bone ingrowth and staining for alkaline phosphatase. The p38 MAPK inhibitor alone decreased alkaline phosphatase staining. When the oral p38 MAPK inhibitor was given and the chamber contained polyethylene particles, there was a suppression of bone ingrowth and alkaline phosphatase staining. In contrast to oral non-steroidal anti-inflammatory drugs (NSAIDs) and local Interleukin-1 receptor antagonist (IL-1ra) administration, the oral p38 MAPK inhibitor alone did not suppress bone formation when given during the initial phase of tissue differentiation. Particle-induced inflammation and the foreign body reaction were not curtailed when the p38 MAPK inhibitor was given simultaneously with particles. Additional experiments are needed to establish the efficacy of p38 MAPK inhibitor administration on mitigating an established inflammatory and foreign body reaction that parallels the clinical situation more closely.

Administration, Oral↗

PubMed2006

Effects of local infusion of OP-1 on particle-induced and NSAID-induced inhibition of bone ingrowth in vivo.

Excessive polyethylene wear particles from joint replacements may lead to periprosthetic osteolysis and loosening. Nonsteroidal anti-inflammatory drugs (NSAIDs) decrease fracture healing and bone ingrowth. We hypothesized that continuous local infusion of OP-1 (BMP-7) would increase local bone formation in the presence of two different adverse stimuli, polyethylene particles, and an oral NSAID. The Drug Test Chamber (DTC) was implanted in the proximal tibia of mature rabbits. The tissue growing into the chamber was exposed to OP-1 solution (110 ng/day), which was infused via an osmotic pump. Infusion of OP-1 alone for 6 weeks enhanced local bone formation in the chamber by 80% (p < 0.05) over infusion of carrier alone. In the presence of polyethylene particles, infusion of OP-1 increased local bone formation by 38% (p < 0.05) over treatment with particles and carrier. Oral administration of NSAID reduced local bone formation by 58% (p < 0.05); this suppressive effect caused by NSAIDS was completely reversed by the infusion of OP-1 (p < 0.05). These findings underline a potential role for local treatment with OP-1 to increase bone formation in the presence of potentially adverse stimuli such as polyethylene wear particles or NSAID use.

Alkaline Phosphatase↗

PubMed2006

The effects of titanium and polymethylmethacrylate particles on osteoblast phenotypic stability.

Wear particles generated following total joint arthroplasty interact with cells at the periprosthetic margin and induce an inflammatory response that contributes to osteolysis, aseptic loosening, and implant failure. This study examined the long-term effects of particles from two commonly implanted materials, titanium (Ti) and polymethylmethacrylate (PMMA), on cell viability and metabolism over a 21-day time course, using the human osteoblast-like cell line MG-63. Addition of particles was not associated with increased cell death or nitric oxide production at the particle concentration chosen. Collagen production was increased with exposure to titanium particles, whereas alkaline phosphatase and osteocalcin expression remained unchanged following exposure to both types of particles. The data show that titanium but not PMMA particles shifts bone cell metabolism to preferentially produce fibrous tissue rather than bone.

Biocompatible Materials↗

PubMed2006

Comparison of VEGF-producing cells in periprosthetic osteolysis.

The pro-angiogenic cytokine vascular endothelial growth factor (VEGF) has been implicated in periprosthetic osteolysis and subsequent aseptic loosening of implants following total hip arthroplasty (THA). The goal of this study was to investigate whether increased VEGF at the bone-implant interface is secondary to a greater number of VEGF-producing cells or to increased VEGF production by individual cells. Real time polymerase chain reaction (RT-PCR) techniques were used to assess the expression of VEGF mRNA (isoforms 121, 165, 189) in periprosthetic tissues from revision THAs. Immunofluorescence was used to determine both differences in overall cellularity and in VEGF-producing cell type (macrophages, fibroblasts, endothelial cells) between patients with periprosthetic osteolysis (OL) and a control group undergoing primary THA for osteoarthritis (OA). Quantitative analysis of VEGF release in periprosthetic membranes via RT-PCR demonstrated no significant difference in the per-cell mRNA production of VEGF isoforms 121 165, or 189 between OL and OA patient groups. Immunofluorescence showed both higher cellularity and higher overall VEGF expression in the OL group. Immunofluorescence also showed a significant increase in macrophages in the OL group, but no significant difference in the proportion of fibroblasts or endothelial cells between the OL and OA groups. Co-localization of CD68+ and CD11b+ macrophage fluorescent signals with VEGF signal was greater in the OL group than in the OA group. Our results demonstrate that increased VEGF in OL periprosthetic tissue compared to OA synovium is correlated to increased numbers of VEGF-producing CD68+ and CD11b+ macrophages. Impact statement: Aseptic loosening, caused in large part by OL, remains the major cause of failed THAs leading to revision surgery. At the bone-implant interface, we found increased numbers of macrophages-cellular mediators of OL-and increased VEGF expression. VEGF may be a possible target for therapeutic intervention in mitigating OL.

Aged↗

PubMed2004

The role of implant alignment on stability and particles on periprosthetic osteolysis--A rabbit model of implant failure.

The study objective was to determine the tissue response to polyethylene and/or titanium particles and the role that these play in peri-prosthetic osteolysis in a rabbit model of implant failure. Twenty-two mature rabbits were used. Unilateral tibial arthroplasty was performed on all of them. The test animals received implants that were intentionally rotationally unstable with reference to the host tibia in order to create a model of failure. The test rabbits were divided into three groups. Group 1 consisted of seven rabbits in which only the carrier was implanted. Group 2 consisted of seven rabbits that received only polyethylene particles suspended in the carrier. Group 3 consisted of eight rabbits that received a mixture of polyethylene and titanium alloy particles suspended in the carrier. The rabbits were sacrificed at 6 months post surgery. The entire knee, together with the immediately surrounding soft tissue, was retrieved. The position of the implant in each rabbit was assessed with reference to its alignment to the tibia. The number of inflammatory, foreign-body reactive cells, the presence of neovascularization, edema, and necrosis in the periprosthetic zones were recorded and assessed in a qualitative and semiquantitative manner. Quantitative histomorphometry was used to determine the proportion of implant surface that interfaced with osseous or fibrous tissue. Also assessed was the thickness and maturity of the fibrous tissue and the endosteal remodeling activity in the peri-implant bone counting both osteoclastic and osteoblastic activity. The results showed that implanted particles and misalignment of the implants combined to produce peri-prosthetic bone resorption. Bone resorption was found to be proportional to the degree of misalignment. The animals that received combined polyethylene/titanium particles had a greater degree of foreign-body and inflammatory response with osteolysis than the other groups. The combination of bio-material particles (polyethylene and titanium alloy) produced a greater degree of bone resorption than the single biomaterial particles (polyethylene). The amount of bone resorption surrounding the implant was directly proportional to the degree of misalignment of the implant.

Alloys↗

PubMed2004

Role of apoptosis in functional luteolysis in the pregnant rabbit corpus luteum: evidence of a role for placental-derived factors in promoting luteal cell survival.

Corpora lutea (CL) were isolated from one rabbit ovary on days 4, 8, 16 (peak luteal function), 28 (functional regression) and 30 of pregnancy and processed for biochemical analysis of DNA integrity. Analysis of DNA integrity revealed the presence of oligonucleosomal fragments in day 28 and day 30 CL but not in day 16 CL. The extent of low molecular weight (<15 kb) DNA labeling was 6.6 +/- 0.84 fold higher in day 30 as compared to day 16 CL (mean +/- SEM; n = 4, P < 0.01). In a second series of experiments, healthy CL collected from day 16 pregnant rabbits were incubated for 2 h in the absence or presence of 250 microg/ml of placental extract (PE) obtained from day 16 and/or day 30 placentas. Analysis of DNA integrity revealed that extensive apoptosis occurred in CL incubated in medium alone and in medium containing day 30 PE. In contrast, day 16 PE significantly suppressed apoptosis vs control (70 +/- 4%). In a third series of experiments, expression of mRNA for bcl-x and bax was measured by Northern analysis of CL treated without and with day 16 PE using cRNA probes for bcl-x and bax developed in our laboratory by RT-PCR. Treatment with PE significantly reduced bax mRNA levels but did not change bcl-x mRNA levels. These studies provide evidence that functional luteolysis in the pregnant rabbit CL is correlated with the occurrence of apoptosis. The data suggest that a factor(s) derived from the placenta may be responsible for the prolongation of CL life span during pregnancy by its ability to alter the bax:bcl -x rheostat and suppress apoptosis.

Animals↗

PubMed2001

CCR7 expression and memory T cell diversity in humans.

CCR7, along with L-selectin and LFA-1, mediates homing of T cells to secondary lymphoid organs via high endothelial venules (HEV). CCR7 has also been implicated in microenvironmental positioning of lymphocytes within secondary lymphoid organs and in return of lymphocytes and dendritic cells to the lymph after passage through nonlymphoid tissues. We have generated mAbs to human CCR7, whose specificities correlate with functional migration of lymphocyte subsets to known CCR7 ligands. We find that CCR7 is expressed on the vast majority of peripheral blood T cells, including most cells that express adhesion molecules (cutaneous lymphocyte Ag alpha(4)beta(7) integrin) required for homing to nonlymphoid tissues. A subset of CD27(neg) memory CD4 T cells from human peripheral blood is greatly enriched in the CCR7(neg) population, as well as L-selectin(neg) cells, suggesting that these cells are incapable of homing to secondary lymphoid organs. Accordingly, CD27(neg) T cells are rare within tonsil, a representative secondary lymphoid organ. All resting T cells within secondary lymphoid organs express high levels of CCR7, but many activated cells lack CCR7. CCR7 loss in activated CD4 cells accompanies CXC chemokine receptor (CXCR)5 gain, suggesting that the reciprocal expression of these two receptors may contribute to differential positioning of resting vs activated cells within the organ. Lymphocytes isolated from nonlymphoid tissues (such as skin, lung, or intestine) contain many CD27(neg) cells lacking CCR7. The ratio of CD27(neg)/CCR7(neg) cells to CD27(pos)/CCR7(pos) cells varies from tissue to tissue, and may correlate with the number of cells actively engaged in Ag recognition within a given tissue.

Biomarkers↗

PubMed2001

Effect of osteogenic protein 1/collagen composite combined with impacted allograft around hydroxyapatite-coated titanium alloy implants is moderate.

This study evaluated the effects of osteogenic protein 1/collagen composite (OP-1/col) mixed with impacted allograft around hydroxyapatite (HA)-coated titanium alloy implants in a canine model. The aim of the study was to test different doses of OP-1 growth factor in a collagen composite for stimulatory effect on allograft incorporation around an implant. Unloaded implants were inserted in each proximal humerus of 16 skeletally mature dogs. The cylindrical implants (4 x 9 mm) coated with HA were initially surrounded by a 3-mm gap into which allograft mixed with OP-1/col was impacted. Two different doses of OP-1 were investigated. In eight animals 325 mg OP-1 protein and 130 mg bovine collagen type I as carrier were mixed with the allograft chips. This composite is identical to the clinically used OP-1 device called Novus. In another eight animals a lower dose of 65 mg OP-1 protein and 130 mg bovine collagen type I was used. Control implants placed in the contralateral humerus were surrounded by allograft mixed with collagen carrier only. The dogs were euthanized at 6 weeks. Implant fixation was determined by push-out testing. Bone ingrowth and bone formation were evaluated by quantitative histomorphometry on serial sections of the bone-implant interface. Impacted allograft together with low-dose OP-1 enhanced bone volume in a zone adjacent to HA-coated titanium alloy implants. The high dose had no effect on bone formation. Mechanical fixation, bone ingrowth, and bone volume in the gap near the original trabecular bone were unaffected by both low and high OP-1/col composite. In this model and observation period, the low dose of OP-1/col composite mixed with impacted allograft has a moderate effect on bone healing around HA-coated implants and no effect on implant fixation.

Animals↗

PubMed2001

In vitro reaction to orthopaedic biomaterials by macrophages and lymphocytes isolated from patients undergoing revision surgery.

Periprosthetic tissues observed at sites of loose total joint implants exhibit abundant macrophages, lymphocytes, fibroblasts and particulate debris. Macrophages phagocytose orthopaedic debris and release proinflammatory cytokines, chemokines, matrix metalloproteinases and other substances. In addition, other cell types present in tissues harvested from the bone-implant interface are thought to influence periprosthetic bone resorption. The present study examined the effects of polymethylmethacrylate (PMMA), cobalt chrome molybdenum alloy (CoCr), and titanium-alloy particle challenge on macrophages co-cultured with lymphocytes in vitro. Potential synergistic effects of lymphocytes on macrophage activation were determined by measuring interleukin-6 and tumor necrosis factor-alpha release following exposure to orthopaedic biomaterial particles. Exposure of macrophages or macrophages co-cultured with lymphocytes to all three types of particles resulted in increased release of interleukin-6 and tumor necrosis factor-alpha at 48 h, when compared to macrophages or macrophages co-cultured with lymphocytes, respectively, cultured in the absence of particles. Lymphocytes isolated from periprosthetic tissues secreted increased basal levels of cytokines relative to peripheral blood lymphocytes. Higher doses of PMMA and titanium-alloy particles stimulated increased levels of cytokine release in the macrophage and macrophage/lymphocyte groups. In contrast, a higher dose of CoCr particles (0.075% v/v) was not as effective as the 0.015% v/v dose, indicating probable CoCr toxicity. The macrophage/lymphocyte co-culture did not show synergism between the two types of cells with respect to cytokine release. T-cells at the bone-implant interface may alter the biological response to particulate debris.

Biocompatible Materials↗

PubMed2001

Interleukin-10 inhibits polymethylmethacrylate particle induced interleukin-6 and tumor necrosis factor-alpha 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. Populations of activated lymphocytes are often seen in periprosthetic membranes. These lymphocytes may modulate the monocyte/macrophage response to particulate debris and influence aseptic loosening. In addition, other immunologic agents, such as interleukin-10, are present in tissues harvested from the bone-implant interface of failed total joint arthroplasties. The present study examined the effects of interleukin-10 on polymethylmethacrylate (PMMA) particle challenged human monocyte/macrophages in vitro. Human monocyte/macrophages isolated from buffy coats of five healthy individuals were exposed to 1-10 microm PMMA particles. Interleukin-10 was added to the monocyte/macrophages with and without the addition of PMMA particles. Interleukin-10-induced alterations in monocyte/macrophage metabolism were determined measuring interleukin-6 and tumor necrosis factor-alpha release by the cells 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. Interleukin-10 reduced the levels of interleukin-6 and tumor necrosis factor-alpha release by macrophages in response to PMMA particles in a dose-dependent manner. At 48 h, particle-induced interleukin-6 release was inhibited by 60 and 90% with 1.0 and 10.0 ng/ml treatments of interleukin-10, respectively. At 48 h, particle-induced tumor necrosis factor-alpha release was inhibited by 58 and 88% with 1.0 and 10.0 ng/ml treatments of interleukin-10, respectively. Interleukin-10 challenge alone did not significantly alter basal interleukin-6 or tumor necrosis factor-alpha release relative to control cultures. The data presented in this study demonstrate that the anti-inflammatory cytokine, interleukin-10, inhibits monocyte/macrophage release of the pro-inflammatory cytokines interleukin-6 and tumor necrosis factor-alpha in response to PMMA particle challenge in vitro.

Biocompatible Materials↗

PubMed2001

Fibroblast expression of C-C chemokines in response to orthopaedic biomaterial particle challenge in vitro.

C-C chemokines are soluble mediators that occur in a periprosthetic granuloma and influence recruitment, localization and activation of inflammatory cells. This study tested effects of titanium and polymethylmethacrylate (PMMA) particles on expression of selected C-C chemokines in cultured human fibroblasts. The C-C chemokines analyzed included monocyte chemoattractant protein-1. 2 (MCP-1. 2), monocyte inflammatory protein-1 alpha (MIP-1 alpha), and regulated on activation, normal T-cell expressed and secreted protein (RANTES). Interleukin-1 beta (IL-1 beta) served as a known stimulator of chemokine release while interleukin-6 (IL-6) expression served as a marker for fibroblast activation. Protein and mRNA signal levels were determined by ELISA and RT-PCR, respectively. The results demonstrated that exposure of fibroblasts to titanium and PMMA particles resulted in increased release of MCP-1 in a dose- and time-dependent manner. After 24 h, titanium particles maximally upregulated MCP-1 release 7-fold while PMMA particles increased MCP-1 levels 2-fold, when compared to unchallenged fibroblasts. MCP-2, MIP-1 alpha and RANTES levels remained unchanged following exposure of fibroblasts to titanium or PMMA particles at any concentration or time point tested. However, IL-1 beta stimulated release of MCP-1, MCP-2, and RANTES, but not MIP-1 alpha from the fibroblasts. IL-1 beta, not particles, exhibited the most prominent effect on MCP-1 mRNA levels. Increased release of MCP-1 from fibroblasts exposed to titanium and PMMA particles coincided with increased release of IL-6. This study suggests that release of chemoattractant factors from fibroblasts localized in periprosthetic membranes enhances the chronic inflammatory process leading to bone resorption and implant loosening.

Bone Cements↗

PubMed2001

Sliding trochanteric osteotomy preserves favorable abductor biomechanics in revision total hip arthroplasty.

The outcome of sliding trochanteric osteotomy in revision total hip arthroplasty was assessed by comparing preoperative and postoperative static radiographic biomechanics and clinical hip abductor function of 22 consecutive operations (20 patients). Preoperative and postoperative pelvic radiographs were reviewed to quantify the biomechanical reconstruction of the hip abductor mechanism. Abductor muscle length and abductor moment arm were increased significantly (P <.05) by the operation. There was a significant (P <.05) increase in maximum degrees of active hip abduction from the preoperative to the postoperative state, an average of 32 months (range, 6-65 months) after surgery. The dysfunction index (a radiographic representation of hip torque) correlated positively (r =.63; P <.05) with active hip abduction. Sliding trochanteric osteotomy improves abductor biomechanics and may protect against trochanteric migration in revision total hip arthroplasty.

Adult↗

PubMed2001

Measurement of perioperative flexion-extension mechanics of the knee joint.

Perioperative knee mechanics currently are evaluated Perioperative knee mechanics currently are evaluated by measuring range of motion. This is an incomplete measurement, however, because the torque applied to achieve the motion is not measured. We hypothesized that a custom goniometer and force transducer could measure the torque required to passively flex a knee through its full range of motion. This measurement was done in the operating room immediately before and after surgery in 20 knees having total knee arthroplasty and 9 having surgery on another limb. Surgery changed the mechanics of 8 knees, whereas unoperated knees remained unchanged. This measurement technique is safe, easy, and repeatable. It improves on the current standard of perioperative knee measurement and can be applied to investigate the effects of surgery and rehabilitation on ultimate knee motion.

Arthroplasty, Replacement, Knee↗

PubMed2001

Preoperative duplex ultrasonography evaluation for deep venous thrombosis in revision hip arthroplasty patients.

In a prospective consecutive series, 53 revision hip arthroplasties were performed in 51 patients. Pre- and postoperative Duplex ultrasonography examinations were reviewed by an independent, experienced radiologist. Three of 51 patients (53 procedures) had evidence of chronic deep venous thrombosis (DVT) or other venous abnormality preoperatively, yielding an incidence of 5.6%. One (1.9%) patient developed an acute DVT postoperatively despite pharmacological and mechanical preventative measures. These results indicate the use of preoperative ultrasonography as a screening tool prior to revision hip arthroplasty is not warranted based on the low incidence of acute or chronic DVT detected preoperatively. Long-term anticoagulation, when necessary, can be based on the findings of a postoperative scan.

Adult↗

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

Lymphocyte CC chemokine receptor 9 and epithelial thymus-expressed chemokine (TECK) expression distinguish the small intestinal immune compartment: Epithelial expression of tissue-specific chemokines as an organizing principle in regional immunity.

The immune system has evolved specialized cellular and molecular mechanisms for targeting and regulating immune responses at epithelial surfaces. Here we show that small intestinal intraepithelial lymphocytes and lamina propria lymphocytes migrate to thymus-expressed chemokine (TECK). This attraction is mediated by CC chemokine receptor (CCR)9, a chemoattractant receptor expressed at high levels by essentially all CD4(+) and CD8(+) T lymphocytes in the small intestine. Only a small subset of lymphocytes in the colon are CCR9(+), and lymphocytes from other tissues including tonsils, lung, inflamed liver, normal or inflamed skin, inflamed synovium and synovial fluid, breast milk, and seminal fluid are universally CCR9(-). TECK expression is also restricted to the small intestine: immunohistochemistry reveals that intense anti-TECK reactivity characterizes crypt epithelium in the jejunum and ileum, but not in other epithelia of the digestive tract (including stomach and colon), skin, lung, or salivary gland. These results imply a restricted role for lymphocyte CCR9 and its ligand TECK in the small intestine, and provide the first evidence for distinctive mechanisms of lymphocyte recruitment that may permit functional specialization of immune responses in different segments of the gastrointestinal tract. Selective expression of chemokines by differentiated epithelium may represent an important mechanism for targeting and specialization of immune responses.

Animals↗

PubMed2000

The effect of a silane coupling agent on the bond strength of bone cement and cobalt-chrome alloy.

Debonding of the cement-implant interface has been hypothesized to be the leading initial indicator of failed total hip prostheses. Many attempts have been made to increase the bond strength of this interface by precoating the implant, increasing the implant's surface roughness, and creating macro-grooves or channels on the implant. However, each of these approaches introduces new complications. This study introduces a unique silane coupling agent used to chemically bond the bone cement to the implant. Cylindrical cobalt-chrome samples were treated with the silane coupling agent, bonded to polymethylmethacrylate, and pushed out to failure. The mean shear strengths were compared to the failure strengths of untreated samples. Half of the specimens were tested immediately following cement curing, and the other half were tested after immersion in saline solution for 60 days. The mean shear strength of the silane-coated samples ranged from 18.2 to 24.1 MPa, and the mean shear strength of the uncoated samples ranged from 7.6 to 15.0 MPa. The increase in strength following silane coating noted in this study may increase the longevity of the implant by decreasing debonding at the interface and, therefore, subsequent failure due to loosening.

Bone Cements↗

PubMed2000

Monocyte migration inhibitory factor synthesis and gene expression in particle-activated macrophages.

This study analysed MIF mRNA and protein expression in human macrophages exposed in vitro to polymethylmethacryate and titanium alloy particles. MIF levels released from macrophages without exposure to particles were in the range of 2-4 ng/ml. Exposure of macrophages to particles as demonstrated increased MIF release at 0. 075%-0.225% v/v particle concentration, which was maximal at 12-24 h. MIF mRNA signal levels in cells with and without particles at a concentration of 0.075% showed no significant differences in a time course experiment. The profile of MIF release in response to increasing particle concentration coincided with increased release of lactate dehydrogenase. The viability of the cells was unchanged by the addition of particles as determined by 3H-thymidine uptake. These data suggest that MIF expression may represent an independent macrophage response to locally high particle concentrations.

Alloys↗