bluuebunny/crossref_metadata_2025_split huggingface dataset:
The angiogenic response to skeletal injury is preserved in the elderly
Authors: Street J. T. , Wang J. H. , Wu Q. D. , Wakai A. , McGuinness A. , Redmond H. P. 
Published: October 2002

AbstractAngiogenesis is essential for normal bone formation and repair. Avascularity characterizes aberrant fracture union in the elderly, while angiogenic mechanisms during cutaneous wound repair are attenuated in aged humans. We hypothesized that skeletal injury results in local (circulating) and systemic (fracture site) ‘angiogenic’ responses and that these reparative mechanisms are attenuated with advanced patient age. This prospective study examined peripheral blood and fracture hematoma from 32 patients, 16 under 40 years and 16 over the age of 75, undergoing emergent surgery for isolated fracture. The angiogenic cytokines vascular endothelial growth factor (VEGF) and platelet‐derived growth factor (PDGF) were assayed. Endothelial cell cultures were supplemented with patient plasma and fracture hematoma and angiogenesis determined in vitro by measuring cell proliferation and blood vessel tube formation. Angiogenesis was determined in vivo using a murine dorsal wound pocket model and quantification of new blood vessel formation after 7 days. We found that all injured patients, irrespective of age, have elevated plasma and fracture hematoma levels of VEGF and PDGF. These elevated cytokine concentrations translate into biologically significant angiogenic effects, in vitro and in vivo. These effects are primarily VEGF mediated and are not dependent on patient age. The biological activity of these growth factors does not diminish with advanced age. Thus skeletal injury does result in local and systemic angiogenic responses whereby angiogenic cytokine availability and activity is preserved in the aged suggesting alternative mechanisms for the development of avascularity in delayed and fracture non‐union in the elderly. © 2001 Orthopaedic Research Society. Published by Elsevier Science Ltd. All rights reserved.
Hydroxyapatite crystals as a local delivery system for cisplatin: adsorption and release of cisplatin in vitro
Authors: Barroug Allal , Glimcher Melvin J. 
Published: October 2002

AbstractThis study describes the characteristics of the in vitro binding and release of the anti‐tumor drug cisplatin by slurries of synthetic hydroxyapatite crystals carried out in aqueous media. The adsorption of cisplatin by slurries of hydroxyapatite and its release were found to depend significantly on the ionic composition of the aqueous media used. At a constant pH of 7.4, significantly more cisplatin is adsorbed by the hydroxyapatite crystals in the slurry from a chloride‐free phosphate buffered solution or a Tris buffered solution than from a buffered phosphate solution containing chloride ions. The amount of hydroxyapatite‐bound cisplatin desorbed into solution was also progressively increased as a function of the increasing concentration of chloride in the equilibrating solution. Very little hydroxyapatite‐bound cisplatin was released from the crystals in either a Tris or phosphate buffer. These results suggest that it is the hydrated derivatives of cisplatin which are involved in the adsorption of cisplatin by hydroxyapatite crystals. The adsorption data can be expressed as a Freundlich isotherm from which the association constant can be calculated. The rate of release of cisplatin bound to crystals of hydroxyapatite is relatively slow even at the maximum concentration of chloride ions in the phosphate buffer. Approximately 33% of the total cisplatin bound to the crystals of hydroxyapatite was released after 4.25 days. An additional 15% of the remaining cisplatin bound to the hydroxyapatite cyrstals was released after an additional equilibration with fresh buffer for two weeks (58% of the total cisplatin originally bound). These findings suggest that cisplatin bound to slurries of hydroxyapatite crystals may be useful in the local treatment of malignant tumors. © 2002 Orthopaedic Research Society. Published by Elsevier Science Ltd. All rights reserved.
Clonality studies in giant cell tumor of bone
Authors: Schwartz H. S. , Eskew J. D. , Butler M. G. 
Published: October 2002

AbstractGenetic studies including chromosome analysis, telomere reduction and telomere activity, DNA microsatellites and loss of heterozygosity (LOH) studies have been performed on giant cell tumor (GCT) of bone however whether this primary skeletal neoplasm represents a monoclonal or polyclonal proliferation is unknown. Utilizing a new assay to study the polymorphic human androgen receptor locus (HUMARA), the ratio of maternal inactive X‐chromosome to the paternal inactive X (Lyon hypothesis) is determined via a methylation – specific polymerase chain reaction (PCR) technique to detect X‐chromosome polymorphisms. Characterization of the genetic tumorigenesis of this unpredictable neoplasm may lend insight into its biological behavior and offer improvements in therapeutic intervention, as new information emerges regarding osteoclastic bone resorption. Seventeen female patients with giant cell tumor of bone had their DNA harvested and their X‐chromosome inactivation pattern and polymorphisms determined and compared to control. A polyclonal proliferation pattern was identified in all informative samples studied. © 2002 Orthopaedic Research Society. Published by Elsevier Science Ltd. All rights reserved.
Subchondral defects in caprine femora augmented with in situ setting hydroxyapatite cement, polymethylmethacrylate, or autogenous bone graft: biomechanical and histomorphological analysis after two‐years
Authors: Welch Robert D. , Berry B. Hudson , Crawford Kevin , Zhang Hong , Zobitz Mark , Bronson Dwight , Krishnan Sumant 
Published: October 2002

AbstractJuxta‐articular defects pose significant challenges due to the high risk of fracture of the subchondral plate and articular cartilage. We evaluated the mechanical and histomorphological repair process of caprine subchondral femoral defects augmented with either a bioresorbable in situ setting hydroxyapatite cement (HAC), polymethylmethacrylate (PMMA), autogenous bone graft (AG), or left empty. Twelve‐mm subchondral defects were made bilaterally in the medial femoral condyles of skeletally mature goats and augmented with a test material or left empty. Femurs were harvested at varying time periods out to 2 years and evaluated for subchondral stiffness and histomorphological indices. Several defects augmented using autograft or left empty sustained focal fracture of the subchondral plate. No HAC or PMMA augmented defects showed evidence of subchondral fracture. The HAC and PMMA augmented defects showed comparable stiffness at all time points. The mean volume fraction of HAC remaining within the defects progressively decreased from 96% at 24 h to 38% at 2 years. The new bone replacing the HAC appeared to have normal physiological architecture and orientation. In situ setting hydroxyapatite cement may be a viable alternative for the repair of subchondral defects with an important advantage that while undergoing gradual resorption and replacement with host bone, mechanical integrity of the skeletal defect is maintained. © 2002 Orthopaedic Research Society. Published by Elsevier Science Ltd. All rights reserved.
Low‐intensity pulsed ultrasound increases the fracture callus strength in diabetic BB Wistar rats but does not affect cellular proliferation
Authors: Gebauer Gregory P. , Lin Sheldon S. , Beam Heather A. , Vieira Pedro , Parsons J. Russell 
Published: October 2002

AbstractType I diabetes mellitus (DM) is associated with impaired fracture healing. Specifically, DM affects multiple phases of fracture healing including early cellular proliferation and late phases resulting in inferior biomechanical properties. Recent studies demonstrated the utility of pulsed low‐intensity ultrasound (US) to facilitate fracture healing. The current study evaluated the effects of daily application of US on mid‐diaphyseal femoral fractures in DM and non‐DM BB Wistar rats. Immunohistochemical staining for PCNA was used to evaluate cellular proliferation at 2, 4, and 7 days post‐fracture. In concordance with previous findings, DM fracture callus demonstrated decreased cellular proliferation. Importantly, the application of US did not significantly alter the proliferation in either DM or control groups. However, mechanical testing revealed significantly greater torque to failure and stiffness in US‐treated DM versus non‐US‐treated DM groups at six weeks post‐fracture. Despite the inability of US to affect the early proliferative phase of fracture healing, its application clearly results in improved mechanical properties during the late phases of healing. These findings suggest a potential role of US as an adjunct for DM fracture treatment. © 2002 Orthopaedic Research Society. Published by Elsevier Science Ltd. All rights reserved.
Expression of smooth muscle actin in osteoblasts in human bone
Authors: Kinner B. , Spector M. 
Published: October 2002

AbstractIt is well known that certain connective tissue cells (viz., dermal fibroblasts) can express the gene for a muscle actin – α‐smooth muscle actin – and can contract. This process contributes to skin wound closure and is responsible for Dupuytren's contracture. The objective of this study was to determine if human osteoblasts can also express the gene for α‐smooth muscle actin. Immunohistochemistry using a monoclonal antibody for α‐smooth muscle actin was performed on human cancellous bone samples obtained from 20 individuals at the time of total joint arthroplasty. The percentages of resting and active osteoblasts on the bone surfaces containing this muscle actin isoform were evaluated. Explants of human bone were also studied for the expression of α‐smooth muscle actin in the tissue and in the outgrowing cells with time in culture. Western blot analysis was performed to quantify the α‐smooth muscle actin content of the outgrowing cells relative to smooth muscle cell controls.Nine ± 2% (mean ± SEM; n = 20) of the cells classified as inactive osteoblasts and 69 ± 3% (n = 19) of the cells identified as active osteoblasts on the bone surface contained α‐smooth muscle actin. This difference was highly statistically significant (Student's t test, p < 0.0001). Similar profiles of α‐smooth muscle actin‐expressing cells were found in explants cultured for up to 12 weeks. Cells forming a layer on the surface of the explants and growing out from them in monolayer also contained α‐smooth muscle actin by immunohistochemistry and Western blot analysis.Human osteoblasts can express the gene for α‐smooth muscle actin. This expression should be considered a phenotypic characteristic of this cell type, conferred by its progenitor cells: bone marrow stromal‐derived stem cells, and perhaps pericytes and smooth muscle cells. © 2002 Orthopaedic Research Society. Published by Elsevier Science Ltd. All rights reserved.
Vascular endothelial growth factor (VEGF)‐induced angiogenesis in herniated disc resorption
Authors: Haro Hirotaka , Kato Tsuyoshi , Komori Hiromichi , Osada Motonobu , Shinomiya Kenichi 
Published: October 2002

AbstractIntervertebral disc herniation is a major cause of low back pain and sciatica. Spontaneous resorption of herniated disc (HD) is frequently detected by magnetic resonance imaging (MRI). Marked infiltration by macrophages and neo‐vascularization are observed upon histogical examination of HD. In addition, enhanced MRI studies suggest that HD resorption occurs more frequently in those completely exposed to the epidural space and that this correlates with their degree of vascularization. We have postulated that the angiogenic factor, vascular endothelial growth factor (VEGF), may be implicated in the neo‐vascularization of HD tissues. Here we demonstrate that VEGF and its receptors VEGFR‐1 and VEGFR‐2 are expressed in human surgical samples of HD. Using a co‐culture system comprised of murine peritoneal macrophages and intervertebral disc tissue as a model of the acute phase of HD developed previously, an increase in macrophage VEGF protein and mRNA expression was observed upon exposure to disc tissue. Tumor necrosis factor alpha (TNF‐α) was required for this induction of VEGF. Use of a novel angiogenesis assay revealed that addition of the conditioned media from the co‐culture system resulted in an increase of vascular tubule formation. This effect was strongly inhibited by anti‐VEGF antibody, but augmented by recombinant VEGF. We conclude that VEGF induction, under the co‐culture conditions tested can result in neo‐vascularization of intervertebral disc tissue and may thus play a role in the resorption of HD. © 2002 Orthopaedic Research Society. Published by Elsevier Science Ltd. All rights reserved.
Predictors of wound infection in hip and knee joint replacement: results from a 20 year surveillance program
Authors: Saleh Khaled , Olson Mary , Resig Scott , Bershadsky Boris , Kuskowski Mike , Gioe Terence , Robinson Harry , Schmidt Richard , McElfresh Edward 
Published: October 2002

AbstractBackground. Deep wound infection (DWI) in total knee (TKA) and total hip (THA) arthroplasty has been shown to highly correlate with superficial surgical site infection (SSSI). Although several studies have reported hospital factors that predispose to SSSI, patient factors have not been clearly elucidated.Methods. All patients undergoing TKA (n = 1181) and THA (n = 1124) surgery during the period 1977–1995 at our institution were observed at the end of a 30‐day post‐operative period. Thirty‐three patients that developed SSSI during this period constituted the study group. The control group was composed of 64 matched subjects that did not develop SSSI. A chart review was applied to abstract DWI cases during the first 18 post‐operative months for the study group and for an average of 6.7 years for the control group (range 5–18.2 years). Potential risk factors for SSSI were used as predictors of SSSI in a logistic regression analysis.Results. During the 18‐month observation period 19 out of the 33 study subjects (58%) developed DWI. No DWI was registered in the control group (the difference was significant, p < 0.0001). Of the nine pre‐operative, five intra‐operative, and five post‐operative factors examined, only hematoma formation (odds ratio = 11.8; p = 0.001) and days of post‐operative drainage (odds ratio = 1.32; p = 0.01) were significant predictors of SSSI. The cases consumed more health care resources at all stages of the medical process.Conclusions. Our results (1) confirm the strong correlation between the probability of developing DWI and SSSI: (2) indicate that hematoma formation and persistent post‐operative drainage increase the risk of SSSI. We hypothesize that post‐operative monitoring of patients for hematoma and persistent drainage enables earlier intervention that may lower the risk of developing SSSI and subsequent DWI. © 2002 Orthopaedic Research Society. Published by Elsevier Science Ltd. All rights reserved.
Recombinant human bone morphogenetic protein‐4 (rhBMP‐4) enhanced posterior spinal fusion without decortication
Authors: Guo Xia , Lee Kwan Man , Law Lai Pang , Chow Hung Kay Daniel , Rosier Randy , Cheng Chung Yiu Jack 
Published: October 2002

AbstractIn posterior spinal fusion, insufficient decortication may decrease the number of bone marrow derived ostoprogenitor stem cells and affect the success of bony fusion. The finding of bone formation through interaction between rhBMP‐4 and non‐marrow derived mesenchymal cells constituted the basis of the current study. The aim is to investigate the possibility of molecular enhancement of posterior spinal fusion by site‐specific application of rhBMP‐4 with or without surgical decortication. Eighteen adult rabbits underwent single level bilateral posterior intertransverse process spinal fusion at L5‐L6, one side with decortication, and the other side without decortication. Two animals underwent sham operation without bone grafts, the other 16 animals were randomly allocated into three groups, using hydroxyapatite‐tricalcium phosphate (HA‐TCP) ceramic blocks augmented with 0, 0.125 and 0.5 mg of rhBMP‐4 respectively. Spinal fusion morphology was evaluated with sequential X‐ray, microradiography and histomorphology. At week 7, complete bony fusion was achieved in none of the groups without rhBMP‐4 irrespective of whether the bony contact surface was decorticated or not. In the groups with low dose rhBMP‐4, complete fusion occurred in two of six un‐decorticated sites (33%) and in three of six (50%) decorticated sites. 100% complete fusion was found in the high dose rhBMP‐4 group independent of surgical decortication. The dorsal cortices of the un‐decorticated transverse processes were replaced by newly formed trabecular bone through biological remodeling. This study suggested that rhBMP‐4 can induce non‐marrow derived mesenchymal cells to differentiate into osteogenic cells and thus enhance the high success rate of posterior spinal fusion in both the decorticated and un‐decorticated model. © 2002 Orthopaedic Research Society. Published by Elsevier Science Ltd. All rights reserved.
The effect of long‐term methylprednisolone treatment on the femoral head in growing pigs
Authors: Drescher Wolf , Li Haisheng , Jensen Søren D. , Ingerslev Jørgen , Hansen Ebbe S. , Hauge Ellen M. , Bünger Cody 
Published: October 2002

AbstractThe effect of long term steroid treatment on coagulation, intraosseous pressure (IOP), femoral head (FH) blood flow, and histology in the normal organism was investigated in this study in growing pigs. From 24 growing female Danish Landrace pigs from 12 litters, 12 animals daily received 100 mg methylprednisolone orally for three months. Their 12 sister pigs served as controls without steroid treatment. Prothrombin time, activated partial thromboplastin time (aPTT), fibrinogen, and antithrombin III levels were recorded in jugular venous blood. Blood flow of the hip regions was measured by means of the radioactive microsphere technique. Metaphyseal and epiphyseal IOP of the left or right proximal femur were measured. Histomorphometry of the left or right FH epiphysis was performed. Major growth inhibition was found in the corticosteroid (CS) treated group. In CS pigs, aPTT was shortened to 50% compared to control pigs. Plasma fibrinogen was higher in the CS animals. Total FH blood flow was not different while regional blood flow in the cranial subregion of the FH epiphysis was higher in the CS group. Metaphyseal and epiphyseal IOP of the proximal femur were not different in the CS animals. Histomorphometrically, cancellous bone volume (23 ± 1% vs. 34 ± 2%; p ≤ 0.001) and bone turnover (10 ± 2% vs. 55 ± 8%; p ≤ 0.001) of the FH epiphysis was lower in the CS than in the control group. The FH epiphysis of the CS animals invariably showed an irregular cartilage‐bone interface with cartilaginous projections into the subchondral bone mainly in its cranial part. In normal growing pigs, long term high dose CS treatment has induced a hypercoagulable state of plasma via the intrinsic pathway of coagulation, cartilaginous projections into FH subchondral bone, FH osteopenia, and reduced bone turnover. Long‐term steroid treatment did not produce FH necrosis or FH IOP alterations in the immature pig model. © 2002 Orthopaedic Research Society. Published by Elsevier Science Ltd. All rights reserved.
RNA splicing mediated by YB‐1 is inhibited by TLS/CHOP in human myxoid liposarcoma cells
Authors: Rapp Timothy B. , Yang Liu , Conrad Ernest U. , Mandahl Nils , Chansky Howard A. 
Published: October 2002

AbstractHuman myxoid liposarcoma contains a characteristic t(12;16) chromosomal translocation that results in fusion of the N‐terminal domain of the translocated in liposarcoma (TLS) protein to the C/EBP homologous protein (CHOP). TLS possesses structural motifs that suggest it may participate in RNA processing. We demonstrate that in human myxoid liposarcoma cells, wild‐type TLS binds to RNA polymerase II (Pol II) via its N‐terminal domain and to the transcription and translation factor Y‐box binding protein‐1 (YB‐1) through its C‐terminal domain. The liposarcoma fusion protein TLS/CHOP retains the ability to bind RNA Pol II but lacks the ability to recruit YB‐1 due to replacement of the C‐terminal domain of TLS by CHOP. In an in vivo splicing assay, YB‐1 promotes splicing of adenovirus E1A pre‐mRNA predominantly to the 13S isoform. The oncogenic TLS/CHOP fusion protein inhibits this splicing function of YB‐1 in a dominant negative manner. When considered in conjunction with studies on other sarcoma fusion proteins, these data suggest that aberrant RNA splicing may be a common feature of human sarcomas. © 2002 Orthopaedic Research Society. Published by Elsevier Science Ltd. All rights reserved.
Gzα deficient mice: enzyme levels in the autonomic nervous system, neuronal survival and effect of genetic background
Authors: Powell Kim L. , Matthaei Klaus I. , Heydon Katharina , Hendry Ian A. 
Published: October 2002

AbstractOur laboratory has generated a genetically mutant mouse in which the alpha subunit of the heterotrimeric GTP binding protein, Gz has been made dysfunctional by homologous recombination to determine its in vivo function. These animals show a characteristic failure to thrive phenotype. Gzα is expressed in a variety of nervous system tissues as well as in the adrenal medulla. We therefore examined the autonomic nervous system of the Gzα deficient mouse by measuring the activity of tyrosine hydroxylase and choline acetyltransferase in the superior cervical ganglia, submaxillary gland and the adrenal medulla. Preliminary results using animals of mixed BALB/c and C57BL/6 strains gave inconsistent results. Further experiments demonstrated differences in the activity of tyrosine hydroxylase and choline acetyltransferase between BALB/c and C57BL/6 mouse strains. The analysis of the pure strains showed a reduction in the size and enzyme levels of the adrenal gland and submaxillary glands of the Gzα deficient mouse suggesting a role for adrenal insufficiency and/or nutritional disorders for the failure to thrive phenotype. The survival of sympathetic and sensory neurons was also examined in the Gzα deficient mouse and in the presence of pertussis toxin, sympathetic but not sensory neuronal survival in Gzα deficient mice was significantly attenuated. This suggests that in vivo other pertussis toxin sensitive G proteins may be recruited to compensate for the loss of Gzα.