Yunshan Liu - Academia.edu (original) (raw)

Papers by Yunshan Liu

Tetrahedron Letters, 1999

A PCP-type catalyst was prepared and examined within the context of intramolecular Heck reactions... more A PCP-type catalyst was prepared and examined within the context of intramolecular Heck reactions. A substrate possessing a 1,4-diene system effectively poisoned the PCP catalyst leading to no reaction. This behavior contrasts with the typical palladium(0) catalyst system.

ChemInform Abstract: Heck Reactions: A Caveat on the Use of Palladium(II) PCP-Type Catalysts

Cheminform, 2010

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was e... more ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Tetrahedron Letters, 1999

A PCP-type catalyst was prepared and examined within the context of intramolecular Heck reactions... more A PCP-type catalyst was prepared and examined within the context of intramolecular Heck reactions. A substrate possessing a 1,4-diene system effectively poisoned the PCP catalyst leading to no reaction. This behavior contrasts with the typical palladium(0) catalyst system.

ChemInform Abstract: Heck Reactions: A Caveat on the Use of Palladium(II) PCP-Type Catalysts

Cheminform, 2010

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was e... more ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Protein Expression and Purification, 2009

Short peptide sequences known as protein transduction domains have become increasingly prevalent ... more Short peptide sequences known as protein transduction domains have become increasingly prevalent as tools to internalize molecules that would otherwise remain extracellular. Here, we determine whether a purified recombinant mammalian intracellular osteogenic factor delivered by a HIV-derived TAT-peptide tag is indeed capable of intracellular localization in a form accessible to interaction with other proteins. We engineered and bacterially expressed a TAT-fusion-cDNA construct of a known osteogenic factor, LIM mineralization protein-1 (LMP-1) involved in the bone morphogenetic protein (BMP) pathway that has the potential to serve as an enhancer of BMP-2 efficacy.

Bone, 2004

Addition of dexamethasone (Dex) to human mesenchymal stem cells (hMSCs) resulted in a 16-fold inc... more Addition of dexamethasone (Dex) to human mesenchymal stem cells (hMSCs) resulted in a 16-fold increase in human bone morphogenetic protein-6 (hBMP-6) mRNA levels 24 h after treatment. Evaluation of luciferase expression after transfection of HeLa cells with hBMP-6 promoter/luciferase reporter constructs indicated that the hBMP-6 promoter activity was contained in a 268-bp region (−1051 to −784 where +1 is the translation start site) over 600 bases 5′ to that previously published. It further showed that the promoter activity is regulated by glucocorticoid treatment. Analysis of RNA from hMSCs and HeLa cells by primer extension, RNase protection, and 5′ RACE further narrowed the location of the transcription start site to an 84-bp region (−940 to −857). To determine whether this start site was regulated in hMSCs, hBMP-6 mRNA levels in control and Dex-treated cells were quantitated by RT-PCR using one primer set in the translated region of the gene and one located just 3′ of the 84-bp region. Both primer sets showed hBMP-6 mRNA levels approximately 16- to 22-fold higher in the Dex-treated cells, demonstrating that hBMP-6 transcription is being regulated by glucocorticoids in the pluripotent hMSCs at the upstream transcription start site.

LMP1, A LIM-Domain Protein, Mediates BMP6 Effects on Bone Formation

Endocrinology, 1998

Glucocorticoids can promote osteoblast differentiation from fetal calvarial cells and bone marrow... more Glucocorticoids can promote osteoblast differentiation from fetal calvarial cells and bone marrow stromal cells. We recently reported that glucocorticoid specifically induced bone morphogenetic protein-6 (BMP-6), a glycoprotein signaling molecule that is a multifunctional regulator of vertebrate development. In the present study, we used fetal rat secondary calvarial cultures to determine genes induced during early osteoblast differentiation as initiated by glucocorticoid treatment. Glucocorticoid, and subsequently BMP-6, was found to induce a novel rat intracellular protein, LIM mineralization protein-1 (LMP-1), that in turn resulted in synthesis of one or more soluble factors that could induce de novo bone formation. Blocking expression of LMP-1 using antisense oligonucleotide prevented osteoblast differentiation in vitro. Overexpression of LMP-1 using a mammalian expression vector was sufficient to initiate de novo bone nodule formation in vitro and in sc implants in vivo. These data demonstrate that LMP-1 is an essential positive regulator of the osteoblast differentiation program as well as an important intermediate step in the BMP-6 signaling pathway.

Cell Biochemistry and Function, 2009

The requirement of large amounts of the recombinant human bone morphogenetic protein-2 (BMP-2) pr... more The requirement of large amounts of the recombinant human bone morphogenetic protein-2 (BMP-2) produces a huge translational barrier for its routine clinical use due to high cost. This leads to an urgent need to develop alternative methods to lower costs and/or increase efficacies for using BMP-2. In this study, we describe the development and optimization of a cell-based assay that is sensitive, reproducible, and reliable in identifying reagents that potentiate the effects of BMP-2 in inducing transdifferentiation of C2C12 myoblasts into the osteoblastic phenotype. The assay is based on a BMP-responsive Smad1-driven luciferase reporter gene. LIM mineralization protein-1 (LMP-1) is a novel intracellular LIM domain protein that has been shown by our group to enhance cellular responsiveness to BMP-2. Our previous report elucidated that the binding of LMP-1 with the WW2 domain in Smad ubiquitin regulatory factor-1 (Smurf1) rescues the osteogenic Smads from degradation. Here, using the optimized cell-based assay, we first evaluated the activity of the recombinantly prepared proteins, LMP-1, and its mutant (LMP-1ΔSmurf1) that lacks the Smurf1-WW2 domain-binding motif. Both the wild type and the mutant proteins were engineered to contain an 11-amino acid HIV-TAT protein derived membrane transduction domain to aid the cellular delivery of recombinant proteins. The cell-based reporter assay confirmed that LMP-1 potentiates the BMP-induced stimulation of C2C12 cells towards the osteoblastic phenotype. The potentiating effect of LMP-1 was significantly reduced when a specific-motif known to interact with Smurf1 was mutated. We validated the results obtained in the reporter assay by also monitoring the expression of mRNA for osteocalcin and alkaline phosphatase (ALP) which is widely accepted osteoblast differentiation marker genes. Finally, we provide further confirmation of our results by measuring the activity of alkaline phosphatase in support of the accuracy and reliability of our cell-based assay. Direct delivery of synthesized protein can be limited by high cost, instability or inadequate post-translational modifications. Thus, there would be a clear benefit for a low cost, cell penetrable chemical compound. We successfully used our gene expression-based assay to choose an active compound from a select group of compounds that were identified by computational screenings as the most likely candidates for mimicking the function of LMP-1. Among them, we selected SVAK-3, a compound that showed a dose-dependent potentiation of BMP-2 activity in inducing osteoblastic differentiation of C2C12 cells. We show that either the full length LMP-1 protein or its potential mimetic compound consistently exhibit similar potentiation of BMP-2 activity even when multiple markers of the osteoblastic phenotype were parallely monitored. Published in 2009 by John Wiley & Sons, Ltd.

Acta Biochimica Et Biophysica Sinica, 2007

LIM mineralization protein-1 (LMP-1) is a novel intracellular osteoinductive protein that has bee... more LIM mineralization protein-1 (LMP-1) is a novel intracellular osteoinductive protein that has been shown to induce bone formation both in vitro and in vivo. LMP-1 contains an N-terminal PDZ domain and three C-terminal LIM domains. In this study, we investigated whether a truncated form of human LMP-1 (hLMP-1[t]), lacking the three C-terminal LIM domains, triggers the differentiation of pluripotent myoblastic C 2 C 12 cells to the osteoblast lineage. C 2 C 12 cells were transiently transduced with Ad5-hLMP-1 (t)-green fluorescent protein or viral vector control. The expression of hLMP-1(t) RNA and the truncated protein were examined. The results showed that hLMP-1(t) blocked myotube formation in C 2 C 12 cultures and significantly enhanced the alkaline phosphatase (ALP) activity. In addition, the expressions of ALP, osteocalcin, and bone morphogenetic protein (BMP)-2 and BMP-7 genes were also increased. The induction of these key osteogenic markers suggests that hLMP-1(t) can trigger the pluripotent myoblastic C 2 C 12 cells to differentiate into osteoblastic lineage, thus extending our previous observation that LMP-1 and LMP-1(t) enhances the osteoblastic phenotype in cultures of cells already committed to the osteoblastic lineage. Therefore, C 2 C 12 cells are an appropriate model system for the examination of LMP-1 induction of the osteoblastic phenotype and the study of mechanisms of LMP-1 action.

Osteoinductive LIM mineralization protein-1 suppresses activation of NF-κB and selectively regulates MAPK pathways in pre-osteoclasts

Bone, 2010

LIM mineralization protein-1 (LMP-1) is an intracellular regulator of bone formation and has been... more LIM mineralization protein-1 (LMP-1) is an intracellular regulator of bone formation and has been shown to be osteoinductive in vitro and in vivo. The effect of LMP-1 on other aspects of bone homeostasis has not been previously studied. In a pilot study we observed that LMP-1 decreased nitric oxide (NO) production in pre-osteoclasts. Here we report a new anti-inflammatory effect of LMP-1 and define its mechanism of action in lipopolysaccharide (LPS)-stimulated RAW 264.7 pre-osteoclasts. We found that LMP-1 significantly inhibited LPS-induced NO production. LMP-1 also effectively inhibited the expression of inducible nitric oxide synthase (iNOS), potently suppressed the transcriptional activity and nuclear translocation of nuclear factor kappa B (NF-kappaB), and prevented the phosphorylation of inhibitor of kappa B (IkappaB). Interestingly, LMP-1 had no effect on Receptor-Activator of Nuclear Factor B Ligand (RANKL)-induced activation of NF-kappaB. Furthermore, LMP-1 had no effect on the LPS-induced phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2), whereas it did attenuate the phosphorylation of c-Jun NH2-terminal kinase (JNK) while enhancing phosphorylation of p38 mitogen-activated protein kinases (p38 MAPK). These results suggest that LMP-1 has an anti-inflammatory effect, and this effect is, at least in part, due to the inhibition of NO production by the suppression of NF-kappaB activation and selective regulation of mitogen-activated protein kinase (MAPK) pathways.

Clinical Orthopaedics and Related Research, 2000

Spine Journal, 2003

The maintenance of interbody space height following anterior lumber interbody fusion is expected ... more The maintenance of interbody space height following anterior lumber interbody fusion is expected to be affected by the choice of spinal implant. METHODS: The InFix and BAK interbody fusion systems were compared through a multi-center FDA IDE. The InFix interbody fusion system (Spinal Concepts, Austin, TX) is comprised of two titanium plates of variable sizes, selected to best fit the geometry of the patients vertebral endplates. A pair of struts, placed at the lateral edges of the disc space and ranging in height from 8 to 16 mm, separate the two plates. Spikes on the endplate (approximately 1.5mm tall) resist implant migration. The system also allows for the restoration of lordosis ranging from 0-18 degrees. Primary inclusion criteria for this radiographic review included DDD at one level at either L4-5 or L5-S1 and failure of non-operative treatment for a minimum of 6 months prior to surgery. Following informed consent, subjects were randomized into one of two groups, InFix vs. BAK in a 2:1 ratio. Radiographs were collected preoperatively, perioperatively and at 1, 6, 12 and 24 months postoperatively. Ninety subjects had at least 12 months of radiographic follow up (65 InFix, 25 BAK), and 69 (of the 90) had 24 months of follow-up (50 InFix, 19 BAK). An independent reviewer assessed all films. Using the lateral view, the far anterior and far posterior interbody space heights were measured at each radiographic interval. These values were normalized to the anteroposterior distance of the superior surface of the inferior vertebral body to eliminate scaling error. Repeated measures analysis of variance were conducted to study the intra-subjects effect of time (pre, peri, 1, 6, 12, and 24 months) and the inter-subjects effects of device and lumbar level. A significance level of 0.05 was established. RESULTS: Surgery caused a significant increase in the anterior and posterior interbody heights, independent of device, with mean increases of 65% and 68% respectively. Between perioperative and the 1-month follow up, anterior height was affected by a significant interaction between the three main effects (pϭ0.041). BAK was associated with a 25% loss of anterior height at L4-L5 and a 10% loss at L5-S1. InFix was associated with a 10% loss of anterior height at L4-L5 and a 13% loss at L5-S1. Posterior height was affected by an interaction of device and time (pϭ0.045), but not level. BAK lost 35% of its posterior height within the first month, while InFix lost 14%. There were no device related effects after the first month. Both devices experiences a 14% decrease in posterior height at L4-5 from month 1 to month 6; similarly posterior height at L5-S1 decreased just 1% during that time. There was no further settling between 6 and 24 months. DISCUSSION: Both InFix and the BAK were associated with some loss of interbody height at the 1-month follow-up but InFix retained more of its initial height. The InFix device is designed to settle as the spikes dig into the vertebral endplates and the amount of settling observed correlates to the geometry of the spikes. CONCLUSIONS: Interbody fusion cages exhibit initial settling with the first postoperative month. Some settling should be expected upon initial weight bearing. Interbody height stabilizes after the sixth postoperative month and out to two years. The BAK is susceptible to losing a significant amount of anterior height at L4-L5 and posterior height at L4-L5 and L5-S1.

Voronoi Cell Finite Element Model for Thermoelastoplastic Deformation in Random Heterogeneous Media

Applied Mechanics Reviews, 1994

A finite element model has been developed for analysis of heterogeneous media, in which second ph... more A finite element model has been developed for analysis of heterogeneous media, in which second phase inclusions are arbitrarily dispersed within a matrix. A mesh generator based on Dirichlet tessellation, discretizes the heterogeneous domain, accounting for the arbitrariness in ...

International Journal for Numerical Methods in Engineering, 1995

In this paper, a new ‘Voronoi cell finite element model’ is developed for solving steady-state he... more In this paper, a new ‘Voronoi cell finite element model’ is developed for solving steady-state heat conduction and micropolar thermoelastic stress analysis problems in arbitrary heterogeneous materials. The method is based on the natural discretization of a multiple phase domain into basic structural elements by Dirichlet Tessellation. Tessellation process results in a network of polygons called Voronoi polygons. In this paper, formulations are developed for treating these polygons as elements in a finite element mesh. Furthermore, a composite Voronoi cell finite element model is developed to account for the presence of a second phase inclusion within a polygonal element. Various numerical examples are executed for validating the effectiveness of this model in the analysis of the temperature and stress fields for micropolar elastic materials. Effective material properties are derived for microstructures containing different distributions of second phase.

Tetrahedron Letters, 1999

A PCP-type catalyst was prepared and examined within the context of intramolecular Heck reactions... more A PCP-type catalyst was prepared and examined within the context of intramolecular Heck reactions. A substrate possessing a 1,4-diene system effectively poisoned the PCP catalyst leading to no reaction. This behavior contrasts with the typical palladium(0) catalyst system.

ChemInform Abstract: Heck Reactions: A Caveat on the Use of Palladium(II) PCP-Type Catalysts

Cheminform, 2010

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was e... more ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Tetrahedron Letters, 1999

A PCP-type catalyst was prepared and examined within the context of intramolecular Heck reactions... more A PCP-type catalyst was prepared and examined within the context of intramolecular Heck reactions. A substrate possessing a 1,4-diene system effectively poisoned the PCP catalyst leading to no reaction. This behavior contrasts with the typical palladium(0) catalyst system.

ChemInform Abstract: Heck Reactions: A Caveat on the Use of Palladium(II) PCP-Type Catalysts

Cheminform, 2010

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was e... more ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Protein Expression and Purification, 2009

Short peptide sequences known as protein transduction domains have become increasingly prevalent ... more Short peptide sequences known as protein transduction domains have become increasingly prevalent as tools to internalize molecules that would otherwise remain extracellular. Here, we determine whether a purified recombinant mammalian intracellular osteogenic factor delivered by a HIV-derived TAT-peptide tag is indeed capable of intracellular localization in a form accessible to interaction with other proteins. We engineered and bacterially expressed a TAT-fusion-cDNA construct of a known osteogenic factor, LIM mineralization protein-1 (LMP-1) involved in the bone morphogenetic protein (BMP) pathway that has the potential to serve as an enhancer of BMP-2 efficacy.

Bone, 2004

Addition of dexamethasone (Dex) to human mesenchymal stem cells (hMSCs) resulted in a 16-fold inc... more Addition of dexamethasone (Dex) to human mesenchymal stem cells (hMSCs) resulted in a 16-fold increase in human bone morphogenetic protein-6 (hBMP-6) mRNA levels 24 h after treatment. Evaluation of luciferase expression after transfection of HeLa cells with hBMP-6 promoter/luciferase reporter constructs indicated that the hBMP-6 promoter activity was contained in a 268-bp region (−1051 to −784 where +1 is the translation start site) over 600 bases 5′ to that previously published. It further showed that the promoter activity is regulated by glucocorticoid treatment. Analysis of RNA from hMSCs and HeLa cells by primer extension, RNase protection, and 5′ RACE further narrowed the location of the transcription start site to an 84-bp region (−940 to −857). To determine whether this start site was regulated in hMSCs, hBMP-6 mRNA levels in control and Dex-treated cells were quantitated by RT-PCR using one primer set in the translated region of the gene and one located just 3′ of the 84-bp region. Both primer sets showed hBMP-6 mRNA levels approximately 16- to 22-fold higher in the Dex-treated cells, demonstrating that hBMP-6 transcription is being regulated by glucocorticoids in the pluripotent hMSCs at the upstream transcription start site.

LMP1, A LIM-Domain Protein, Mediates BMP6 Effects on Bone Formation

Endocrinology, 1998

Glucocorticoids can promote osteoblast differentiation from fetal calvarial cells and bone marrow... more Glucocorticoids can promote osteoblast differentiation from fetal calvarial cells and bone marrow stromal cells. We recently reported that glucocorticoid specifically induced bone morphogenetic protein-6 (BMP-6), a glycoprotein signaling molecule that is a multifunctional regulator of vertebrate development. In the present study, we used fetal rat secondary calvarial cultures to determine genes induced during early osteoblast differentiation as initiated by glucocorticoid treatment. Glucocorticoid, and subsequently BMP-6, was found to induce a novel rat intracellular protein, LIM mineralization protein-1 (LMP-1), that in turn resulted in synthesis of one or more soluble factors that could induce de novo bone formation. Blocking expression of LMP-1 using antisense oligonucleotide prevented osteoblast differentiation in vitro. Overexpression of LMP-1 using a mammalian expression vector was sufficient to initiate de novo bone nodule formation in vitro and in sc implants in vivo. These data demonstrate that LMP-1 is an essential positive regulator of the osteoblast differentiation program as well as an important intermediate step in the BMP-6 signaling pathway.

Cell Biochemistry and Function, 2009

The requirement of large amounts of the recombinant human bone morphogenetic protein-2 (BMP-2) pr... more The requirement of large amounts of the recombinant human bone morphogenetic protein-2 (BMP-2) produces a huge translational barrier for its routine clinical use due to high cost. This leads to an urgent need to develop alternative methods to lower costs and/or increase efficacies for using BMP-2. In this study, we describe the development and optimization of a cell-based assay that is sensitive, reproducible, and reliable in identifying reagents that potentiate the effects of BMP-2 in inducing transdifferentiation of C2C12 myoblasts into the osteoblastic phenotype. The assay is based on a BMP-responsive Smad1-driven luciferase reporter gene. LIM mineralization protein-1 (LMP-1) is a novel intracellular LIM domain protein that has been shown by our group to enhance cellular responsiveness to BMP-2. Our previous report elucidated that the binding of LMP-1 with the WW2 domain in Smad ubiquitin regulatory factor-1 (Smurf1) rescues the osteogenic Smads from degradation. Here, using the optimized cell-based assay, we first evaluated the activity of the recombinantly prepared proteins, LMP-1, and its mutant (LMP-1ΔSmurf1) that lacks the Smurf1-WW2 domain-binding motif. Both the wild type and the mutant proteins were engineered to contain an 11-amino acid HIV-TAT protein derived membrane transduction domain to aid the cellular delivery of recombinant proteins. The cell-based reporter assay confirmed that LMP-1 potentiates the BMP-induced stimulation of C2C12 cells towards the osteoblastic phenotype. The potentiating effect of LMP-1 was significantly reduced when a specific-motif known to interact with Smurf1 was mutated. We validated the results obtained in the reporter assay by also monitoring the expression of mRNA for osteocalcin and alkaline phosphatase (ALP) which is widely accepted osteoblast differentiation marker genes. Finally, we provide further confirmation of our results by measuring the activity of alkaline phosphatase in support of the accuracy and reliability of our cell-based assay. Direct delivery of synthesized protein can be limited by high cost, instability or inadequate post-translational modifications. Thus, there would be a clear benefit for a low cost, cell penetrable chemical compound. We successfully used our gene expression-based assay to choose an active compound from a select group of compounds that were identified by computational screenings as the most likely candidates for mimicking the function of LMP-1. Among them, we selected SVAK-3, a compound that showed a dose-dependent potentiation of BMP-2 activity in inducing osteoblastic differentiation of C2C12 cells. We show that either the full length LMP-1 protein or its potential mimetic compound consistently exhibit similar potentiation of BMP-2 activity even when multiple markers of the osteoblastic phenotype were parallely monitored. Published in 2009 by John Wiley & Sons, Ltd.

Acta Biochimica Et Biophysica Sinica, 2007

LIM mineralization protein-1 (LMP-1) is a novel intracellular osteoinductive protein that has bee... more LIM mineralization protein-1 (LMP-1) is a novel intracellular osteoinductive protein that has been shown to induce bone formation both in vitro and in vivo. LMP-1 contains an N-terminal PDZ domain and three C-terminal LIM domains. In this study, we investigated whether a truncated form of human LMP-1 (hLMP-1[t]), lacking the three C-terminal LIM domains, triggers the differentiation of pluripotent myoblastic C 2 C 12 cells to the osteoblast lineage. C 2 C 12 cells were transiently transduced with Ad5-hLMP-1 (t)-green fluorescent protein or viral vector control. The expression of hLMP-1(t) RNA and the truncated protein were examined. The results showed that hLMP-1(t) blocked myotube formation in C 2 C 12 cultures and significantly enhanced the alkaline phosphatase (ALP) activity. In addition, the expressions of ALP, osteocalcin, and bone morphogenetic protein (BMP)-2 and BMP-7 genes were also increased. The induction of these key osteogenic markers suggests that hLMP-1(t) can trigger the pluripotent myoblastic C 2 C 12 cells to differentiate into osteoblastic lineage, thus extending our previous observation that LMP-1 and LMP-1(t) enhances the osteoblastic phenotype in cultures of cells already committed to the osteoblastic lineage. Therefore, C 2 C 12 cells are an appropriate model system for the examination of LMP-1 induction of the osteoblastic phenotype and the study of mechanisms of LMP-1 action.

Osteoinductive LIM mineralization protein-1 suppresses activation of NF-κB and selectively regulates MAPK pathways in pre-osteoclasts

Bone, 2010

LIM mineralization protein-1 (LMP-1) is an intracellular regulator of bone formation and has been... more LIM mineralization protein-1 (LMP-1) is an intracellular regulator of bone formation and has been shown to be osteoinductive in vitro and in vivo. The effect of LMP-1 on other aspects of bone homeostasis has not been previously studied. In a pilot study we observed that LMP-1 decreased nitric oxide (NO) production in pre-osteoclasts. Here we report a new anti-inflammatory effect of LMP-1 and define its mechanism of action in lipopolysaccharide (LPS)-stimulated RAW 264.7 pre-osteoclasts. We found that LMP-1 significantly inhibited LPS-induced NO production. LMP-1 also effectively inhibited the expression of inducible nitric oxide synthase (iNOS), potently suppressed the transcriptional activity and nuclear translocation of nuclear factor kappa B (NF-kappaB), and prevented the phosphorylation of inhibitor of kappa B (IkappaB). Interestingly, LMP-1 had no effect on Receptor-Activator of Nuclear Factor B Ligand (RANKL)-induced activation of NF-kappaB. Furthermore, LMP-1 had no effect on the LPS-induced phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2), whereas it did attenuate the phosphorylation of c-Jun NH2-terminal kinase (JNK) while enhancing phosphorylation of p38 mitogen-activated protein kinases (p38 MAPK). These results suggest that LMP-1 has an anti-inflammatory effect, and this effect is, at least in part, due to the inhibition of NO production by the suppression of NF-kappaB activation and selective regulation of mitogen-activated protein kinase (MAPK) pathways.

Clinical Orthopaedics and Related Research, 2000

Spine Journal, 2003

The maintenance of interbody space height following anterior lumber interbody fusion is expected ... more The maintenance of interbody space height following anterior lumber interbody fusion is expected to be affected by the choice of spinal implant. METHODS: The InFix and BAK interbody fusion systems were compared through a multi-center FDA IDE. The InFix interbody fusion system (Spinal Concepts, Austin, TX) is comprised of two titanium plates of variable sizes, selected to best fit the geometry of the patients vertebral endplates. A pair of struts, placed at the lateral edges of the disc space and ranging in height from 8 to 16 mm, separate the two plates. Spikes on the endplate (approximately 1.5mm tall) resist implant migration. The system also allows for the restoration of lordosis ranging from 0-18 degrees. Primary inclusion criteria for this radiographic review included DDD at one level at either L4-5 or L5-S1 and failure of non-operative treatment for a minimum of 6 months prior to surgery. Following informed consent, subjects were randomized into one of two groups, InFix vs. BAK in a 2:1 ratio. Radiographs were collected preoperatively, perioperatively and at 1, 6, 12 and 24 months postoperatively. Ninety subjects had at least 12 months of radiographic follow up (65 InFix, 25 BAK), and 69 (of the 90) had 24 months of follow-up (50 InFix, 19 BAK). An independent reviewer assessed all films. Using the lateral view, the far anterior and far posterior interbody space heights were measured at each radiographic interval. These values were normalized to the anteroposterior distance of the superior surface of the inferior vertebral body to eliminate scaling error. Repeated measures analysis of variance were conducted to study the intra-subjects effect of time (pre, peri, 1, 6, 12, and 24 months) and the inter-subjects effects of device and lumbar level. A significance level of 0.05 was established. RESULTS: Surgery caused a significant increase in the anterior and posterior interbody heights, independent of device, with mean increases of 65% and 68% respectively. Between perioperative and the 1-month follow up, anterior height was affected by a significant interaction between the three main effects (pϭ0.041). BAK was associated with a 25% loss of anterior height at L4-L5 and a 10% loss at L5-S1. InFix was associated with a 10% loss of anterior height at L4-L5 and a 13% loss at L5-S1. Posterior height was affected by an interaction of device and time (pϭ0.045), but not level. BAK lost 35% of its posterior height within the first month, while InFix lost 14%. There were no device related effects after the first month. Both devices experiences a 14% decrease in posterior height at L4-5 from month 1 to month 6; similarly posterior height at L5-S1 decreased just 1% during that time. There was no further settling between 6 and 24 months. DISCUSSION: Both InFix and the BAK were associated with some loss of interbody height at the 1-month follow-up but InFix retained more of its initial height. The InFix device is designed to settle as the spikes dig into the vertebral endplates and the amount of settling observed correlates to the geometry of the spikes. CONCLUSIONS: Interbody fusion cages exhibit initial settling with the first postoperative month. Some settling should be expected upon initial weight bearing. Interbody height stabilizes after the sixth postoperative month and out to two years. The BAK is susceptible to losing a significant amount of anterior height at L4-L5 and posterior height at L4-L5 and L5-S1.

Voronoi Cell Finite Element Model for Thermoelastoplastic Deformation in Random Heterogeneous Media

Applied Mechanics Reviews, 1994

A finite element model has been developed for analysis of heterogeneous media, in which second ph... more A finite element model has been developed for analysis of heterogeneous media, in which second phase inclusions are arbitrarily dispersed within a matrix. A mesh generator based on Dirichlet tessellation, discretizes the heterogeneous domain, accounting for the arbitrariness in ...

International Journal for Numerical Methods in Engineering, 1995

In this paper, a new ‘Voronoi cell finite element model’ is developed for solving steady-state he... more In this paper, a new ‘Voronoi cell finite element model’ is developed for solving steady-state heat conduction and micropolar thermoelastic stress analysis problems in arbitrary heterogeneous materials. The method is based on the natural discretization of a multiple phase domain into basic structural elements by Dirichlet Tessellation. Tessellation process results in a network of polygons called Voronoi polygons. In this paper, formulations are developed for treating these polygons as elements in a finite element mesh. Furthermore, a composite Voronoi cell finite element model is developed to account for the presence of a second phase inclusion within a polygonal element. Various numerical examples are executed for validating the effectiveness of this model in the analysis of the temperature and stress fields for micropolar elastic materials. Effective material properties are derived for microstructures containing different distributions of second phase.