bluuebunny/crossref_metadata_2025_split huggingface dataset:
Differential apoptotic response of J774 macrophages to alumina and ultra‐high‐molecular‐weight polyethylene particles
Authors: Petit Alain , Catelas Isabelle , Antoniou John , Zukor David J. , Huk Olga L. 
Published: October 2002

AbstractWe recently identified apoptosis in in vitro wear particle‐stimulated macrophages. The recent explosion of interest in apoptosis lies in the fact that it is under positive and negative regulation through evolutionary conserved biochemical pathways. It may also be possible to modulate macrophage apoptosis in the treatment of periprosthetic osteolysis. The purpose of this study was to compare the macrophage response to identically sized particles of alumina ceramic (Al2O3) and ultra‐high‐molecular‐weight polyethylene (UHMWPE) in terms of TNF‐α release and induction of apoptosis. J774 mouse macrophages were incubated for 0–24 h in the presence of Al2O3 and UHMWPE particles. TNF‐α release was measured by ELISA; Poly(ADP‐ribose)polymerase (PARP) and caspase‐3 expression was analyzed by Western blot; DNA fragmentation (DNA laddering) was visualized on agarose gel containing ethidium bromide. Al2O3 particles induced TNF‐α release after 4 h incubation with concentrations reaching 483 and 800 pg/ml after 24 h with 125 and 250 particles/macrophage, respectively (control = 161 pg/ml) (P < 0.05 vs. control). The same concentrations of UHMWPE particles induced a much larger and significant TNF‐α release after only 1 h incubation, increasing up to 6250 pg/ml after 24 h (P < 0.05 vs. control). Western blot analysis demonstrated that the active caspase‐3 fragment (17 kDa) and the proteolytic PARP fragment (85 kDa) were expressed after 2 h incubation with 125 and 250 Al2O3 particles/macrophage. The active caspase‐3 and the PARP fragment had lower expression and appeared after a longer incubation time (8 h) with 125 and 250 UHMWPE particles/macrophage. Finally, DNA fragmentation (DNA laddering) was observed after 16 h with 125 and 250 particles of Al2O3 per macrophage whereas no laddering was induced by UHMWPE particles even after 24 h incubation. This study shows that although both Al2O3 and UHMWPE particles induce TNF‐α release, this stimulation was much greater (8–10 times higher) with UHMWPE than A12O3 (P < 0.05 vs. control). As well, the induction of apoptosis, as measured by activation of caspase‐3, PARP cleavage and DNA laddering, is different for these two particles, being faster and more important with Al2O3 than UHMWPE. We hypothesize that the ability of Al2O3 to induce macrophage apoptosis may explain the lower TNF‐α release observed with these particles and explain the differences seen in osteolysis patterns of ceramic–ceramic (CC) vs. metal–polyethylene (Mpe) articulations. In conclusion, apoptosis may be a major internal mechanism to decrease macrophage activity and may be a desired therapeutic endpoint. The identification of an apoptosis‐related pathway in the macrophage response to ceramic particles provides crucial data for a rational approach in the treatment and/or prevention of periprosthetic osteolysis. © 2002 Orthopaedic Research Society. Published by Elsevier Science Ltd. All rights reserved.
Temporal expression patterns of BMP receptors and collagen II (B) during periosteal chondrogenesis
Authors: Sanyal Arunik , Oursler Merry Jo , Clemens Victoria R. , Fukumoto Takumi , Fitzsimmons James S. , O'Driscoll Shawn W. 
Published: October 2002

AbstractArticular cartilage has a limited ability to repair itself. Periosteal grafts have chondrogenic potential and are used clinically to repair defects in articular cartilage. An organ culture model system for in vitro rabbit periosteal chondrogenesis has been established to study the molecular events of periosteal chondrogenesis in vitro. In this model, bone morphogenetic protein‐2 (BMP2) mRNA expression was found to be upregulated in the first 12 h. BMPs usually transduce their signals through a receptor complex that includes type II and either type IA or type IB BMP receptors. Receptors IA and IB play distinct roles during limb development. We have examined the temporal expression patterns for the mRNAs of these receptors using our experimental model. The mRNA expression patterns of these three BMP receptors differed from one another in periosteal explants during chondrogenesis. When these explants were cultured under chondrogenic conditions (agarose suspension with TGF‐β1 added to the media for the first 2 days), the expression of BMPRII mRNA and that of BMPRIA mRNA varied only slightly and persisted over a long time. In contrast, the expression of BMPRIB mRNA was upregulated within 12 h, peaked at day 5, and fell to a level that was barely detected beyond day 21. Moreover, the expression of BMPRIB mRNA preceded that of collagen type IIB mRNAs, a marker for matrix‐depositing chondrocytes. These data support a role for coordinate expression of BMP2 and its receptors early during periosteal chondrogenesis. © 2002 Orthopaedic Research Society. Published by Elsevier Science Ltd. All rights reserved.
Upregulation of basal TGFβ1 levels by EMF coincident with chondrogenesis – implications for skeletal repair and tissue engineering
Authors: Aaron Roy K. , Wang Shuo , Ciombor Deborah McK. 
Published: October 2002

AbstractMembers of the TGFβ/BMP gene family regulate cartilage and bone development. These genes are re‐expressed in bone repair and are thought to mediate chondro‐ and osteoprogenitor cell differentiation. These observations have led to a therapeutic strategy of introducing these growth factors into experimental cartilage and bone defects. Therapeutic efficacy, however, has been limited by diffusion or inactivation of these growth factors from the desired site and by the inability to deliver sustained concentrations of growth factors. This study demonstrates an increase in basal TGFβ mRNA and protein levels in association with chondrogenic differentiation in endochondral ossification. mRNA is increased by 158%; protein by 23%, and cells immunopositive for TGFβ by 343% at maximal TGFβ expression. Importantly, the pattern of TGFβ expression is preserved throughout the developmental sequence. Our data suggest that the exposure to a specific electromagnetic field (EMF) enhances, but does not disorganize, chondrogenesis and endochondral calcification as well as the normal physiologic expression of TGFβ. The ability to increase TGFβ at a moderately low dose for sustained periods of time without disorganizing its physiology suggests the ability to establish temporal concentration gradients of growth factors for the purpose of stimulating skeletal repair. © 2002 Orthopaedic Research Society. Published by Elsevier Science Ltd. All rights reserved.
Serum cartilage‐derived retinoic acid‐sensitive protein (CD‐RAP) levels in Swarm rat chondrosarcoma
Authors: Yonekawa Masahiro , Kondo Seiji , Sugiura Hideshi , Kobayashi Kenji , Watanabe Tsuyoshi , Kimata Koji , Sandell L. J. , Iwata Hisashi 
Published: October 2002

AbstractCartilage‐derived retinoic acid‐sensitive protein (CD‐RAP) is a new protein that was isolated from bovine articular chondrocytes and human melanoma cell lines (melanoma inhibitory protein or MIA). In normal tissue its expression is limited to cartilage, and in morbid tissue to melanoma, chondrosarcoma, and breast cancer. Serum levels of CD‐RAP/MIA correlate with the progression of malignant melanoma, but there have been no reports on chondrosarcoma. Here, it was first demonstrated by RT‐PCR and immuno‐histological methods that CD‐RAP was expressed in tissue from a Swarm rat chondrosarcoma that was used as an experimental model. The course following tumor transplantation and changes in serum CD‐RAP after tumor excision were then observed to investigate whether serum CD‐RAP could be used as a marker of tumor activity. Consequently, serum CD‐RAP in control rats tended to decrease as the animal grew, whereas it rose in proportion to tumor proliferation in rats that had received a tumor graft. Serum CD‐RAP levels dropped rapidly following excision of the tumor in a group of tumor‐excised rats. In those rats which had a recurrence following excision of the tumor, serum CD‐RAP rose prior to the appearance of the tumor. Serum CD‐RAP thus sensitively reflected tumor onset and proliferation, so that it appeared to be an effective marker of tumor activity for Swarm rat chondrosarcoma. © 2002 Orthopaedic Research Society. Published by Elsevier Science Ltd. All rights reserved.
Delayed tendon reattachment does not reverse atrophy and fat accumulation of the supraspinatus — an experimental study in rabbits
Authors: Matsumoto Fujio , Uhthoff Hans K. , Trudel Guy , Loehr Joachim F. 
Published: October 2002

AbstractMuscle atrophy and fat accumulation occur after rotator cuff tearing. Whether these changes are reversible after a successful repair is still unknown. Imaging allows only a semi‐quantitative assessment of muscle atrophy and fat deposition. As only experimental studies permit a quantification of both, a unilateral detachment and wrapping in a polyvinylidine fluoride membrane of the supraspinatus was done in 22 rabbits. After 12 weeks, the polyvinylidine fluoride membrane was removed in 10 rabbits and the tendon inserted into a bony trough. The opposite shoulder served as control. All rabbits were killed at 24 weeks. Accumulation of fat on the muscle surface as well as between the muscle fascicles and occasionally in the sarcoplasm was increased in both experimental groups when compared to controls (non‐reattached 12.8%, reattached 23.5% vs controls 5.4%; all p < 0.005). The muscle atrophy was significant (non‐reattached 9.2 ml, reattached 9.1 ml vs controls 10.7 ml; both p < 0.005). Neither atrophy nor fat accumulation were reversed by surgical reattachment of the supraspinatus tendon. On the contrary, the fat accumulation was higher in the reattached group (p < 0.005). The trauma of reattachment, the delay between detachment and reattachment or an insufficient duration of recovery may have contributed to both, the lack of reversibility of supraspinatus atrophy and fat accumulation. © 2002 Orthopaedic Research Society. Published by Elsevier Science Ltd. All rights reserved.
Effects of different exposures of hyperbaric oxygen on ligament healing in rats
Authors: Ishii Yoshimasa , Ushida Takashi , Tateishi Tetsuya , Shimojo Hitoshi , Miyanaga Yutaka 
Published: October 2002

AbstractHyperbaric oxygen (HBO) is a method of augmenting, intermittently, oxygen availability to tissues. We examined the effect of three different HBO exposures on the healing of experimentally induced ligament lacerations in the right hind limb of 44 male Wistar rats. Animals were divided into four groups after ligament injury: (a) control group, animals breathed room air at 1 ATA (atmosphere absolute) in a hyperbaric chamber for 60 min; (b) HBO treatment at 1.5 ATA for 30 min once a day, (c) HBO treatment at 2 ATA for 30 min once a day, (d) 2 ATA for 60 min once a day. At 14 days post‐ligament injury, we compared the ligaments of the four treatment groups for gross appearance, histology and expression of pro‐α(I) mRNA by northern hybridization. Our results indicate that HBO was effective in promoting ligament healing compared to control (p < 0.01). Of these three exposures, HBO at 2 ATA for 60 min was the most effective, resulting in enhanced extra‐cellular matrix deposition as measured by collagen synthesis. © 2002 Orthopaedic Research Society. Published by Elsevier Science Ltd. All rights reserved.
Assessment of specific mRNA levels in cartilage regions in a lapine model of osteoarthritis
Authors: Le Graverand Marie‐Pierre Hellio , Eggerer Jonna , Vignon Eric , Otterness Ivan G. , Barclay Leona , Hart David A. 
Published: October 2002

AbstractOsteoarthritis (OA) is the most common form of arthritis and patients with meniscal and ligament injuries of the knee are at high risk to develop the disease. The purpose of this study was to evaluate molecular and structural changes occurring in four articular cartilage (AC) regions from the knees of anterior cruciate ligament (ACL)‐transected rabbits at 3 and 8 weeks post‐surgery. Rabbit AC from the lateral and medial femoral condyles (LFC and MFC) as well as from the medial and lateral tibial plateau (MTP and LTP) were processed for histology and for semi‐quantitative reverse transcriptase‐polymerase chain reaction (RT‐PCR) analysis for a subset of relevant molecules (collagen II, aggrecan, biglycan, decorin, fibromodulin, MMP‐1,‐3,‐13, and TIMP‐1). While the most severe histological changes were observed in the MTP starting as early as 3 weeks post‐ACL transection based on Mankin scores, histological examination demonstrated a progression of osteoarthritic changes in the MFC from 3 to 8 weeks post‐surgery. In contrast, very few changes were observed within both the LFC and LTP, and these changes did not worsen with increasing time after surgery. The water content increased significantly in the MFC at 8 weeks post‐ACL transection and at both 3 and 8 weeks post‐ACL transection in the MTP. Significant decreases in DNA content were observed for the MFC, LTP and MTP at 8 weeks post‐ACL transection. Total RNA yields from the MFC and MTP were significantly elevated at 8 weeks post‐ACL transection, while in the lateral compartment total RNA was unchanged following ACL transection. Analysis of mRNA levels for a subset of matrix molecules, proteinases and proteinase inhibitors, by RT‐PCR demonstrated significant region‐specific changes at the mRNA level following ACL transection. These results show that following ACL transection, complex molecular, as well as structural changes occur early in cartilage and that the observed changes are both region‐specific and time‐dependent. © 2002 Orthopaedic Research Society. Published by Elsevier Science Ltd. All rights reserved.
Coordinated expression of scleraxis and Sox9 genes during embryonic development of tendons and cartilage
Authors: Asou Yoshinori , Nifuji Akira , Tsuji Kunikazu , Shinomiya Kenichi , Olson Eric N. , Koopman Peter , Noda Masaki 
Published: October 2002

AbstractEmbryonic development of tendons is in close association with that of cartilage and bone. Although these tissues are derived from mesenchymal progenitor cells which also give rise to muscle and fat, their fates clearly diverse in early embryonic stages. Transcription factors may play pivotal roles in the process of determination and differentiation of tendon cells as well as other cells in the skeletal system. Scleraxis, a basic helix‐loop‐helix (bHLH) type transcription factor, is expressed in mesenchymal progenitors that later form connective tissues including tendons. Sox9 is an HMG‐box containing transcription factor, which is expressed at high levels in chondrocytes. We hypothesized that the two transcription factors regulate the fate of cells that interact with each other at the interface between the two tissues during divergence of their differentiation pathways. To address this point, we investigated scleraxis and Sox9 mRNA expression during mouse embyogenesis focusing on the coordinated development of tendons and skeletons. In the early stage of mesenchymal tissue development at 10.5 d.p.c., scleraxis and Sox9 transcripts were expressed in the mesenchymal progenitor cells in the appendicular and axial mesenchyme. At 11.5 d.p.c., scleraxis transcripts were observed in the mesenchymal tissue surrounding skeletal primordia which express Sox9. From this stage, scleraxis expression was closely associated with, but distinct from, formation of skeletal primordia. At 13.5 d.p.c., scleraxis was expressed broadly in the interface between muscle and skeletal primordia while Sox9 expression is confined within the early skeletal primordia. Then, at 15.5 d. p.c., scleraxis transcripts were more restricted to tendons. These observations revealed the presence of temporal and spatial association of scleraxis expression during embryonic development of tendon precursor cells in close association with that of Sox9 expression in chondrogenic cells in skeletal tissues. © 2002 Orthopaedic Research Society. Published by Elsevier Science Ltd. All rights reserved.
Quantitative computed tomography estimates of the mechanical properties of human vertebral trabecular bone
Authors: Kopperdahl David L. , Morgan Elise F. , Keaveny Tony M. 
Published: October 2002

AbstractThe objective of this study was to report our quantitative computed tomography (QCT) density‐mechanical property regressions for trabecular bone for use in biomechanical modelling of the human spine. Cylindrical specimens of human vertebral trabecular bone (from T10 to L4) were cored from 32 cadavers (mean ± SD age = 70.1 ± 16.8; 13 females, 19 males) and scanned using QCT. Mechanical tests were conducted using a protocol that minimized end‐artifacts over the apparent density range tested (0.09–0.38 g/ cm3). To account for the presence of multiple specimens per donor in this data set, donor was treated as a random effect in the regression model. Mean modulus (319 ± 189 MPa) was higher and mean yield strain (0.78 ± 0.06%) was lower than typical values reported previously due to minimization of the end‐artifact errors. QCT density showed a strong positive correlation with modulus (n = 76) and yield stress (r2 = 0.90–0.95, n = 53, p < 0.001). There was a weak positive linear correlation with yield strain (r2 = 0.58, n = 53, p = 0.07). Prediction errors, incurred when estimating modulus or strength for specimens from a new donor, were 30–36% of the mean values of these properties. Direct QCT density‐mechanical property regressions gave more precise predictions of mechanical properties than if physically measured wet apparent density was used as an intermediate variable to predict mechanical properties from QCT density. Use of these QCT density‐mechanical property regressions should improve the fidelity of QCT‐based biomechanical models of the human spine for whole bone and bone‐implant analyses. © 2002 Orthopaedic Research Society. Published by Elsevier Science Ltd. All rights reserved.
Dobutamine echocardiography in idiopathic dilated cardiomyopathy: clinical and prognostic implications
Authors: Pinamonti Bruno , Perkan Andrea , Di Lenarda Andrea , Gregori Dario , Sinagra Gianfranco 
Published: October 2002

AbstractThe dobutamine echocardiographic test (DET) is frequently used in coronary artery disease to detect viable myocardium, but few data are available about its role in idiopathic dilated cardiomyopathy (IDCM). The aims of this study were to evaluate the clinical role of DET and the prognostic implications of the ‘contractile reserve’ in patients with IDCM treated with optimal medical therapy, including β‐blockade (BB). A total of 51 patients with IDCM underwent DET at diagnosis. A positive response to DET (DET+) was judged to be a significant increase (≥10 points) in left ventricular ejection fraction (LVEF) with a peak value ≥40%, and a reversed restrictive left ventricular filling pattern (RFP) if present at baseline study. Improvement at follow‐up was defined according to combined clinical and echo‐Doppler criteria. In all, 22 patients (43%) were classified as DET+. DET+ patients were less symptomatic (P<0.001), with lower heart rate (P<0.01), less enlarged left and right ventricles (P<0.0001 and P<0.05), higher LVEF (P‐0.0001), less frequent RFP (P‐0.01), and lower pulmonary pressure (P<0.01). At follow‐up (34±16 months), 21 patients had improved, while four had died and seven had received a transplant. Among clinical data, NYHA classes I–II (OR‐0.25, P‐0.07) and BB dosage (OR‐0.97, P<0.005) were significantly associated with higher transplant‐free survival at multivariate analysis. The addition of DET+ (OR‐0.34, P<0.05) showed a moderate but significant improvement of sensitivity, but the predictive power of the model remained low (sensitivity, 0.67; specificity, 0.55). Absence of left bundle branch block (OR‐0.27, P<0.01) and BB dosage (OR‐1.03, P<0.005), but not DET+, were predictive of improvement. In patients with IDCM, DET response is associated with a more favourable outcome, since it suggests an earlier stage of the disease. However, in the light of our data, the incremental prognostic power of DET response compared to clinical evaluation at enrolment, despite being significant, seems to be of limited clinical value. Further studies should be carried out in order to clarify the prognostic value of DET in IDCM patients.
Increased myocardial expression of osteopontin in patients with advanced heart failure
Authors: Stawowy Philipp , Blaschke Florian , Pfautsch Peter , Goetze Stephan , Lippek Frank , Wollert‐Wulf Brigitte , Fleck Eckart , Graf Kristof 
Published: October 2002

AbstractThe expression of the adhesion protein osteopontin (OP) is associated with cardiac hypertrophy and is significantly increased after transition to heart failure in experimental animal models. We, therefore, hypothesized that OP could be upregulated in heart failure in humans. In the present study, we investigated the expression of OP in myocardial biopsies obtained from patients with heart failure due to dilated cardiomyopathy (mean LVEF ‐ 30.3±4.4%, mean±S.D., n ‐ 10, group A) compared to patients with a normal left‐ventricular ejection fraction (mean LVEF ‐ 61±11.2%, n ‐ 9; group B). Myocardial immunoreactivity for OP was examined using two different antibodies against OP. The expression of cardiac myocyte OP was significantly upregulated in group A in comparison to group B (P<0.0001). Both groups also displayed OP immunoreactivity in non‐myocytes, including vascular smooth muscle cells and cardiac fibroblasts (P ‐ not significant). Statistical analysis revealed a significant correlation of increased OP immunoreactivity in cardiac myocytes of patients with impaired left ventricular function, assessed by hemodynamic data (LVEF, RVEF, LVESVI, LVEDVI and LVEDP, R ‐ −0.828, −0.671, 0.751, 0.685 and 0.461, respectively; all P<0.05). Furthermore, OP expression correlated with cardiac myocyte hypertrophy (mean diameter 21.0±1.8 μm in group A and 16.6±2.1 μm in group B; P<0.0001). In conclusion, the present study indicates, that factors and/or mechanisms involved in heart failure in patients with dilated cardiomyopathy, lead to induction of OP expression in humans.
Prevalence of chronic heart failure in Southwestern Europe: the EPICA study
Authors: Ceia Fátima , Fonseca Cândida , Mota Teresa , Morais Humberto , Matias Fernando , de Sousa António , Oliveira António Gouveia ,   on behalf of the EPICA Investigators
Published: October 2002

AbstractAimTo estimate the prevalence of chronic heart failure (CHF) in mainland Portugal in 1998.Methods and populationA community‐based epidemiological survey involving subjects attending primary care centres selected by a combined two‐stage sampling and stratified procedure. General practitioners (GPs) randomly selected in proportion to the population of the District, evaluated subjects attending primary care centres aged over 25 years, recruited consecutively and stratified by age. CHF cases were identified according to the Guidelines of the European Society of Cardiology for CHF diagnosis.Results5434 eligible subjects were evaluated by 365 GPs; 551 patients with CHF were identified. The overall prevalence and 95% CI of CHF in mainland Portugal is 4.36% (3.69–5.02%), 4.33% in males (3.19–5.46%), and 4.38% in females (3.64–5.13%). Age‐specific CHF prevalence was as follows: 1.36% in the 25–49 years‐old group (0.39–2.33%), 2.93% in the 50–59 years‐old group (5.58–9.37%), 7.63% in the 60–69 years‐old group (5.58–9.37%), 12.67% in the 70–79 years‐old group (10.73–14.6%), and 16.14% in group over 80 years old (13.81–18.47%). The prevalence of CHF due to systolic dysfunction was 1.3% and the prevalence of CHF with normal systolic function was 1.7%.ConclusionsThe overall prevalence of CHF in Portugal was slightly higher than that of other European studies and increases sharply with age. The prevalence of CHF due to systolic dysfunction is very similar to that reported by other recent European studies. The differences found may correspond to differences in methodology rather than actual differences in the population.