bluuebunny/crossref_metadata_2025_split huggingface dataset:
Miranda, a protein involved in neuroblast asymmetric division, is associated with embryonic centrosomes of Drosophila melanogaster
Authors: Mollinari Cristiana , Lange Bodo , González Cayetano 
Published: October 2002

AbstractMiranda, a highly coiled‐coil protein, has been shown to be one of the key components necessary for the differential segregation of fate‐determining factors during neurogenesis in Drosophila embryos. The multidomain protein Miranda, by segregating the transcription factor Prospero, guarantees the generation of cell diversity during the formation of the embryonic nervous system. While looking for new molecular components of the centrosome in Drosophila embryos, we have isolated a short isoform of Miranda. An antibody was raised directed against the central coiled‐coil region of Miranda, and the pattern of expression of the protein was studied in details throughout Drosophila development. Here, we show that Miranda has a broad pattern of expression and is a rather ubiquitous molecule. Immunofluorescence on syncytial Drosophila embryos shows that Miranda has a dynamic redistribution and is associated with centrosomes. Electron microscopy on purified syncytial centrosomes shows that Miranda is located on the pericentriolar material along with γ‐tubulin. Taken all together, our data indicate for the first time that Miranda belongs to a growing class of proteins that concentrate at the centrosome in a cell‐cycle and stage‐specific manner. The observations that Miranda has a broad range of expression, as well as a dynamic and cell‐cycle dependent subcellular localization, suggest that it may have alternative functions outside the embryonic nervous system. These potential new functions are discussed in this paper.
The impact of strategic operations management decisions on community hospital performance
Authors: Li Ling X. , Benton W.C. , Leong G.Keong 
Published: October 2002

AbstractOver the past decade, 10% of community hospitals have closed. In this challenging time, our study presents hospital administrators with some valuable information that can help improve community hospitals’ performance. The purpose of this paper is to develop a strategic operations management model that links long‐term service choices, intermediate operations decisions, and hospital performance given the structural constraints of location, size, and medical teaching status. Data collected from 151 community hospitals are used to test the model. The research identifies strategic operations management decisions in the US community hospitals, shows their causal relationships, and identifies their effects on hospital performance. Specifically, we find that intermediate infrastructural operations decisions affect a community hospital’s cost, quality, and financial performance after the structural decisions of location and size have set the stage. Our study also reveals that community hospitals have adopted new staff and demand management decisions in response to the market needs.
Weight‐bearing alters the expression of collagen types I and II, BMP 2/4 and osteocalcin in the early stages ofdistraction osteogenesis
Authors: Radomisli Timothy E. , Moore Douglas C. , Barrach Hans J. , Keeping Hugh S. , Ehrlich Michael G. 
Published: October 2002

AbstractThis study was performed to investigate the effect of loading on the biology of newly forming bone during limb lengthening. Unilateral 2.0 mm femoral lengthenings were performed in 20 male Sprague Dawley rats. Half (n = 10) of the animals were allowed to bear weight freely, while the other half were prevented from weight‐bearing via an ipsilateral through‐knee amputation. The animals in each group were sacrificed after one (n = 5) or four (n = 5) days of consolidation (post‐operative days seven and 10, respectively). In situ hybridization for osteocalcin and collagen I, and antibody staining for collagen II and BMP 2/4 were used to evaluate the molecular influence of loading.There was more new bone in the distraction gap of the weight‐bearing animals than there was in the non‐weight‐bearing animals. BMP 2/4 expression, and the messages for collagen I and osteocalcin, were more abundant in tissue from the weight‐bearing animals; collagen II was higher in the non‐weight‐bearing animals. This suggests that early regenerate tissue is capable of responding to loading, and that weight‐bearing appears to stimulate intramembranous ossification. These findings support the concept of early weight‐bearing after limb lengthening.
Relative roles of microdamage and microfracture in the mechanical behavior of trabecular bone
Authors: Yeh Oscar C. , Keaveny Tony M. 
Published: October 2002

AbstractCompared to trabecular microfracture, the biomechanical consequences of the morphologically more subtle trabecular micro‐damage are unclear but potentially important because of its higher incidence. A generic three‐dimensional finite element model of the trabecular bone microstructure was used to investigate the relative biomechanical roles of these damage categories on reloading elastic modulus after simulated overloads to various strain levels. Microfractures of individual trabeculae were modeled using a maximum fracture strain criterion, for three values of fracture strain (2%, 8%, and 35%). Microdamage within the trabeculae was modeled using a strain‐based modulus reduction rule based on cortical bone behavior. When combining the effects of both microdamage and microfracture, the model predicted reductions in apparent modulus upon reloading of over 60% at an applied apparent strain of 2%, in excellent agreement with previously reported experimental data. According to the model, up to 80% of the trabeculae developed microdamage at 2% apparent strain, and between 2% and 10% of the trabeculae were fractured, depending on which fracture strain was assumed. If microdamage could not occur but microfracture could, good agreement with the experimental data only resulted if the trabecular hard tissue had a fracture strain of 2%. However, a high number of fractures (10% of the trabeculae) would need to occur for this case, and this has not been observed in published damage morphology studies. We conclude therefore that if the damage behavior of trabecular hard tissue is similar to that of cortical bone, then extensive microdamage is primarily responsible for the large loss in apparent mechanical properties that can occur with overloading of trabecular bone. © 2001 Orthopaedic Research Society. Published by Elsevier Science Ltd. All rights reserved.
Osteogenic protein‐1 induced bone formation in an infected segmental defect in the rat femur
Authors: Chen Xinqian , Kidder Louis S. , Lew William D. 
Published: October 2002

AbstractThe goal of this study was to use a segmental defect model in the rat femur to determine if osteogenic protein‐1 (OP‐1) is capable of inducing bone formation in the presence of bacterial contamination. A 6 mm segmental defect was surgically created and stabilized with a polyacetyl plate and Kirschner wires in one femur in each of 126 Sprague–Dawley rats. The animals were divided into eight groups in which the defect was either left untreated, or subjected to various combinations of OP‐1 (11 or 50 μg), lyophilized bovine type I collagen (carrier for the OP‐1), and 105 colony‐forming units of Staphylococcus aureus. The animals were euthanized at either 2, 4, or 9 weeks. Quantitative radiographic and histologic analyses were performed on the harvested tissue. The initial contamination progressed to infection in all animals receiving bacteria, as determined by qualitative bacteriology. There was very little, if any, bone formation in the untreated defects, and in the contaminated defects with or without collagen carrier. Bone formation was significantly greater in contaminated defects with either dose of OP‐1, compared with contaminated defects without OP‐1. The 50 μg dose of OP‐1 induced significantly more bone formation than the 11 μg dose, both with and without bacteria. This investigation has demonstrated that OP‐1 maintains its osteoinductive capability in a contaminated segmental defect. OP‐1 may potentially be used in the clinical management of contaminated fractures. © 2002 Orthopaedic Research Society. Published by Elsevier Science Ltd. All rights reserved.
Integrin expression by human osteoblasts cultured on degradable polymeric materials applicable for tissue engineered bone
Authors: El‐Amin Saadiq F. , Attawia Mohamed , Lu Helen H. , Shah Asist K. , Chang Richard , Hickok Noreen J. , Tuan Rocky S. , Laurencin Cato T. 
Published: October 2002

AbstractThe use of biodegradable polymers in the field of orthopaedic surgery has gained increased popularity, as surgical pins and screws, and as potential biological scaffolds for repairing cartilage and bone defects. One such group of polymers that has gained considerable attention are the polyesters, poly(lactide‐co‐glycolide) (PLAGA) and polylactic acid (PLA), because of their minimal tissue inflammatory response, favorable biocompatibility and degradation characteristics. The objective of this study was to evaluate human osteoblastic cell adherence and growth on PLAGA and PLA scaffolds by examining integrin receptor (α2, α3, α4, α5, α6 and β1) expression. Primary human osteoblastic cells isolated from trabecular bone adhered efficiently to both PLAGA and PLA, with the rate of adherence on PLAGA comparable to that of control tissue culture polystyrene (TCPS), and significantly higher than on PLA polymers at 3, 6 and 12 h. Human osteoblastic phenotypic expression, alkaline phosphatase (ALP) activity was positive on both degradable matrices, whereas osteocalcin levels were significantly higher on cells grown on PLAGA than on PLA composites. Interestingly, the integrin subunits, α2, α3, α4, α5, α6 and β1 were all expressed at higher levels by osteoblasts cultured on PLAGA than those on PLA as analyzed by westerns blots and by flow cytometry. Among the integrins, α2, α5 and β1 showed the greatest difference in levels between the two surfaces. Thus, both PLA and PLAGA support osteoblastic adhesion and its accompanying engagement of integrin receptor and expression of osteocalcin and ALP. However PLAGA consistently appeared to be a better substrate for osteoblastic cells based on these parameters. This study is one of the first to investigate the ability of primary human osteoblastic cells isolated from trabecular bone to adhere to the biodegradable polymers PLAGA and PLA, and to examine the expression of their key adhesion receptors (integrins) on these substrates. © 2002 Orthopaedic Research Society. Published by Elsevier Science Ltd. All rights reserved.
Tissue transglutaminase localization and activity regulation in the extracellular matrix of articular cartilage
Authors: Summey Brett T. , Graff Ronald D. , Lai Thung‐Sheng , Greenberg Charles S. , Lee Greta M. 
Published: October 2002

AbstractTissue transglutaminase (tTG) catalyzes a Ca2+‐dependent transglutaminase (TGase) activity which cross‐links proteins and stabilizes many tissues [C.S. Greenberg et al. FASEB J. 5 (1991) 3071]. Because cartilage is subjected to great stress in vivo, an enzyme that strengthens and stabilizes tissue could play an integral role in maintaining cartilage integrity. The purpose of this study was to determine if active tTG is present in the extracellular matrix (ECM) of adult human osteoarthritic articular cartilage. Using a TGase activity assay along with immunolabeling for tTG of cartilage sections, TGase activity and tTG immunoreactivity were localized in the ECM in cartilage sections, predominantly in the superficial layer. Previous in vitro studies have demonstrated that the Mg‐GTP complex inhibits the TGase activity of tTG [T.S. Lai et al. J. Biol. Chem. 273 (1998) 1776]. To investigate the in situ regulation of the TGase activity of tTG, a TGase activity assay was done with a dose response of GTP, measuring incorporation of fluorescein cadaverine. TGase activity was inhibited by GTP in a similar manner as in vitro. These results not only confirm tTG presence in the ECM, but also indicate tTG as the major TGase activity of the ECM. Secondly, the study provides a possible mechanism by which extracellular tTG is regulated in vivo. © 2002 Orthopaedic Research Society. Published by Elsevier Science Ltd. All rights reserved.
Estrogen regulation of growth and alkaline phosphatase expression by cultured human bone marrow stromal cells
Authors: Holzer Gerold , Einhorn Thomas A. , Majeska Robert J. 
Published: October 2002

AbstractEstrogen has been reported to regulate the growth and differentiation of cultured murine osteoprogenitor cells in bone marrow stroma. This study tested the ability of 17β‐estradiol (E2) to regulate growth and expression of alkaline phosphatase (ALP), an osteoblastic differentiation marker, in strains of normal human bone marrow stromal cells derived from different donors. In eight strains examined, E2 at 1 and 10 nM produced at most modest effectxs on growth and ALP activity. Growth inhibition, seen in 4 of the 8 strains, was more common than stimulation (2 of the 8 strains); the greatest observed E2 effect was an inhibition of ca. 50%. E2 altered ALP activity less dramatically than cell growth. Differences from control in total ALP per culture were seen in only two strains; one was a reduction, one an increase. Colony forming assays were used to determine if E2 changed the proportion of ALP‐expressing cells in marrow stromal cell cultures. In contrast to growth experiments, ALP expression under colony forming conditions (200 cells per 35 mm‐diameter well) was dependent on the type of serum supplementation used. Under permissive conditions using medium supplemented with 10% charcoal‐treated fetal bovine serum, 10 nM E2 increased the number of ALP‐positive colonies (cfu‐ap) but not the total number of colonies formed (cfu‐f). When cells cultured in the presence or absence of 10 nM E2 were replated at colony forming densities, significantly higher proportions of cfu‐ap were found in 2 of 6 strains examined, while pretreatment with E2 affected the number of cfu‐f in only 1 of the 6 strains. Similar results were obtained when colony formation was carried out in the presence of dexamethasone and ascorbate, although these agents themselves increased the formation of both cfu‐f and cfu‐ap. These results show that the direct effects of E2 on human marrow stromal cells are small and vary depending on the cell strain and on the experimental conditions; however, the E2 actions observed in this study were consistent with reports that E2 exerts direct actions on osteoblasts and osteoblast progenitor cells that favor rather than suppress their phenotypic expression. © 2002 Orthopaedic Research Society. Published by Elsevier Science Ltd. All rights reserved.
Quantitative cartilage imaging of the human hind foot: Precision and inter‐subject variability
Authors: Al‐Ali Dina , Graichen Heiko , Faber Sonja , Englmeier Karl‐Hans , Reiser Maximilian , Eckstein Felix 
Published: October 2002

AbstractAlterations of ankle cartilage are observed in degenerative and inflammatory joint disease, but cartilage cannot be directly visualized by radiography. The purpose of this study was therefore to analyze the feasibility and precision of quantitative cartilage imaging in the human hind foot (talocrural, talotarsal, and intertarsal joints), and to report the inter‐subject variability for cartilage volume, thickness and surface areas. The feet of 16 healthy volunteers were imaged using a 3D gradient‐echo magnetic resonance imaging sequence with water‐excitation. After interpolation to a resolution of 1 ± 0.125 ± 0.125 mm3 the cartilage plates were segmented, and the cartilage volume, thickness, and surface areas determined. The precision (four repeated measurements) was examined in eight volunteers, the RMS average CV% being 2.1% to 10.9% in single joint surfaces, and ⩽ 3% for the cumulative values of all joints. The mean cartilage thickness ranged from 0.57 ± 0.08 (navicular surface) to 0.89 ± 0.19 mm (trochlear surface for tibia). In conclusion this study shows that it is feasible to quantify thin cartilage layers in the hind foot under in vivo imaging conditions, and that the precision errors are substantially smaller than the inter‐subject variability in healthy subjects. © 2002 Orthopaedic Research Society. Published by Elsevier Science Ltd. All rights reserved.
Identification of the metalloproteinase stromelysin in the physis
Authors: Armstrong Ann L. , Barrach Hans J. , Ehrlich Michael G. 
Published: October 2002

AbstractFor long bone growth to occur, calcification of the matrix must commence in the lower hypertrophic zone of the growth plate. It is generally accepted that physeal proteoglycans help regulate mineralization, and that at least in vitro, intact proteoglycans can inhibit mineralization. Thus degradation of proteoglycan may be a necessary step prior to calcification. Previous work in our laboratory has demonstrated the presence of neutral metallo‐proteases in the growth plate with highest levels in the hypertrophic zone, where calcification occurs.Stromelysin (MMP‐3) is a connective tissue matrix‐degrading enzyme. It was formerly known as proteoglycanase and is generally considered to be one of the major proteoglycan degrading enzymes in cartilage. Stromelysin is implicated in cartilage destruction in osteoarthritis and may also be involved in tissue remodeling in the physis. Our goal was to determine if the neutral protease previously reported by the authors in the physis was stromelysin.In this study we used Western blots and antibodies to stromelysin and to the stromelysin cleavage site in aggrecan, the most common form of proteoglycan, to demonstrate the presence of stromelysin in the bovine physis. When an antibody raised against the stromelysin cleavage site of aggrecan (FVDIPEN) was incubated with a Western blot, which had been run with aggrecan extracted from bovine physes, a positive reaction resulted. This suggests that there is stromelysin degradation in vivo in the physis. Two different polyclonal antibodies to stromelysin gave positive results on Western blots of purified media from growth plate cultures indicating that stromelysin is produced in vitro in culture. These antibodies also reacted with active stromelysin.The presence of stromelysin in the physis implicates it in physeal physiology. The concentration of its activity in the lower hypertrophic zone and zone of provisional calcification suggests that it may be particularly important in mineralization. © 2002 Orthopaedic Research Society. Published by Elsevier Science Ltd. All rights reserved.
Chronic changes in rabbit retro‐patellar cartilage and subchondral bone after blunt impact loading of the patellofemoral joint
Authors: Ewers Benjamin J. , Weaver Brian T. , Sevensma Eric T. , Haut Roger C. 
Published: October 2002

AbstractAnimal models of acute joint injury are useful for study of changes in joint tissues that may eventually lead to degradative disease. Our laboratory has developed a joint trauma model using a single blunt impact to the patellofemoral joint of rabbits and documented softening of retro‐patellar cartilage and thickening of its underlying bone out to 12 months post‐trauma. In the present study, we examined changes in these joint tissues out to 36 months post‐impact. Forty‐nine Flemish giant rabbits were impacted on the right patellofemoral joint and sacrificed at one of six times: 0, 4.5, 7.5, 12, 24, and 36 months post‐impact. A 30% reduction in the compressive modulus of traumatized retro‐patellar cartilage occurred at 4.5 months versus the contralateral, non‐impacted limb and remained at this reduced level out to 36 months. The fluid permeability of traumatized cartilage also increased over time from baseline and versus the non‐impacted limb. Tissue thickness increased slightly at 4.5 months and then decreased over time to a 45% difference from baseline at 36 months post‐trauma. While impacted cartilage revealed a significantly greater length of surface fissuring than contralateral, non‐impacted cartilage, no time‐dependent changes were evident in this study. Moreover, the number and depth of these impact surface lesions did not change as a function of time. Finally, the histological analyses indicated that the thickness of underlying subchondral bone increased over time from baseline and versus that in the non‐impacted limb. This long‐term study suggested an association between a decrease in the characteristic time constant of traumatized cartilage and thickening of the underlying subchondral bone. Any potential cause and effect relationship, however, must be investigated in future studies. © 2002 Orthopaedic Research Society. Published by Elsevier Science Ltd. All rights reserved.
Reliability of detecting prosthesis/cement interface radiolucencies in total hip arthroplasty
Authors: Zhang Yongde , Putnam Aaron W. , Heiner Anneliese D. , Callaghan John J. , Brown Thomas D. 
Published: October 2002

AbstractA laboratory study assessed the reliability of detecting radiolucencies at the prosthesis/cement interface in femoral components for total hip replacement. Radiolucencies (thicknesses = 0.1, 0.3, 0.5 and 0.7 mm) were created by randomly masking non‐tip Gruen zones (six per stem) in a group of 72 matte‐finish femoral components. Only half of all Gruen zones were masked. The femoral components were reproducibly implanted in composite fiberglass replicate femurs. Anteroposterior and lateral radiographs taken using conventional techniques were then presented to 10 experienced readers, who scored each of 432 non‐tip Gruen zones for radiolucency presence or absence. The series‐average radiolucency detection rate was 47.1%, with a breakdown of 9.8%, 20.7%, 69.8% and 88.0% for radiolucency thicknesses of 0.1, 0.3, 0.5 and 0.7 mm, respectively. The false positive rate was 7.5%. The findings argue strongly that in many or most instances, initial cement‐prosthesis debonding is not reliably detected from conventional plain film radiographs. Radiolucencies of at least 0.7 mm width are necessary to be accurately detectable by most viewers. © 2002 Orthopaedic Research Society. Published by Elsevier Science Ltd. All rights reserved.
Clinical trials update: The Heart Protection Study, IONA, CARISA, ENRICHD, ACUTE, ALIVE, MADIT II and REMATCH
Authors: Louis Amala A. , Manousos I. Renata , Coletta Alison P. , Clark Andrew L. , Cleland John G.F. 
Published: October 2002

AbstractThis article continues a series of reports summarising recent research developments of particular interest to those involved in the management of patients with heart failure. A number of relevant presentations were made at the American Heart Association Scientific Sessions in Anaheim, California, between 11–14 November 2001. Summaries of the following Clinical Trials are included: The Heart Protection Study, IONA, CARISA, ENRICHD, ACUTE, ALIVE, MADIT II and REMATCH.
Short‐term effects of sinus rhythm restoration in patients with lone atrial fibrillation: a hormonal study
Authors: Jourdain P. , Bellorini M. , Funck F. , Fulla Y. , Guillard N. , Loiret J. , Thebault B. , Sadeg N. , Desnos M. 
Published: October 2002

AbstractIt is well known that atrial fibrillation can lead to heart failure, and is attributed to rapid ventricular rate (tachycardia‐induced cardiomyopathy). Some recent studies suggest the possible existence of an intrinsic left‐ventricular factor related to atrial fibrillation, irrespective of other elements. In order to demonstrate the implication of this factor, we measured B‐type Natriuretic Peptide, known as a functional marker of left‐ventricular dysfunction, in 40 consecutive patients with chronic non‐valvular atrial fibrillation, with low ventricular rate and absence of clinical heart failure or echocardiographic left‐ventricular dysfunction. In all patients, Brain Natriuretic Peptide (BNP) plasma level was high and dramatically decreased 24 h after external electrical cardioversion (61.4 pg/ml before cardioversion, 23.5 pg/ml 1 day after cardioversion, P<0.002). Our study demonstrates that atrial fibrillation, in absence of high ventricular rate, induces an asymptomatic cardiac alteration that is not detectable by echocardiography.