bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cell repopulation in vascularized bone grafts
Authors: Muramatsu Keiichi , Bishop Allen T. 
Published: October 2002

AbstractFollowing vascularized bone autografts, osteocyte viability is largely maintained. Viable cells within a graft may be surviving graft‐derived cells, their progeny, or host‐derived cells from circulation or surrounding bone. This study was conducted to define the process of cell repopulation, within vascularized bone grafts. Using inbred Lewis rats, 30 female vascularized tibial bones were transplanted to syngeneic male recipients and 45 male grafts were transplanted to female recipients. Twenty‐five female recipients were immunosuppressed with FK506 to prevent rejection caused by Y‐chromosome related antigens. The grafts were assessed up to 24 weeks post‐transplant by radiography, histology and semi‐quantitative polymerase chain reaction (PCR) using both Y‐chromosome and autosome gene‐specific primers. The female to male isograft transplants were useful to measure low levels of repopulation with host‐derived cells, while male to female transplants more accurately quantified higher levels of cellular replacement. No host‐derived cells were detected in the transplanted bone before six weeks. Thereafter, the ratio of host‐derived cells gradually increased. By 24 weeks only 0.1–1.0% of graft‐derived cells remained in the transplanted tibias. This study demonstrates that Y‐chromosome‐specific PCR is a useful tool to detect the cell lineage and cell repopulation following rat sex‐mismatch vascularized bone grafting. Our results showed that donor cells in vascularized bone grafts were gradually repopulated with recipient cells. Correlation with histologic findings suggests that the periosteal hypertrophy observed by six weeks post‐transplant results from graft‐derived cells, while later remodeling is associated with host‐derived cells. © 2002 Orthopaedic Research Society. Published by Elsevier Science Ltd. All rights reserved.
Adherent endotoxin mediates biological responses of titanium particles without stimulating their phagocytosis
Authors: Bi Yanming , Collier Terry O. , Goldberg Victor M. , Anderson James M. , Greenfield Edward M. 
Published: October 2002

AbstractAseptic loosening of orthopaedic implants is thought to be primarily due to stimulation of cytokine production by wear particles from the implants. The cytokines increase osteoclast differentiation, leading to osteolysis and implant loosening. Accumulating evidence indicates that adherent endotoxin mediates the biological responses induced by the wear particles. One mechanism by which adherent endotoxin may act is by increasing phagocytosis of the wear particles. To test this hypothesis, the effect of adherent endotoxin on phagocytosis of titanium particles was determined. First, we developed reliable confocal and fluorescence microscopy methods to examine both the attachment and internalization steps of phagocytosis. Use of these methods showed that adherent endotoxin does not detectably alter the rate or the extent of phagocytosis of titanium particles by RAW 264.7 cells. Despite this lack of an effect on phagocytosis, adherent endotoxin dramatically increases the ability of RAW 264.7 cells to produce TNF‐α and induce osteoclast differentiation. Thus, adherent endotoxin mediates these biological responses by a mechanism that does not rely on increased phagocytosis. These results also demonstrate that phagocytosis is not sufficient to induce cytokine production and osteoclast differentiation but do not rule out the possibility that phagocytosis is required for induction of these responses by titanium particles with adherent endotoxin. © 2002 Orthopaedic Research Society. Published by Elsevier Science Ltd. All rights reserved.
Biomechanical consequences of PCL deficiency in the knee under simulated muscle loads—an in vitro experimental study
Authors: Li Guoan , Gill Thomas J. , DeFrate Louis E. , Zayontz Shay , Glatt Vaida , Zarins Bertram 
Published: October 2002

AbstractThe mechanism of chronic degeneration of the knee after posterior cruciate ligament (PCL) injury is still not clearly understood. While numerous biomechanical studies have been conducted to investigate the function of the PCL with regard to antero‐posterior stability of the knee, little has been reported on its effect on the rotational stability of the knee. In this study, eight cadaveric human knee specimens were tested on a robotic testing system from full extension to 120° of flexion with the PCL intact and with the PCL resected. The antero‐posterior tibial translation and the internal‐external tibial rotation were measured when the knee was subjected to various simulated muscle loads. Under a quadriceps load (400 N) and a combined quadriceps/hamstring load (400/200 N), the tibia moved anteriorly at low flexion angles (below 60°). Resection of the PCL did not significantly alter anterior tibial translation. At high flexion angles (beyond 60°), the tibia moved posteriorly and rotated externally under the muscle loads. PCL deficiency significantly increased the posterior tibial translation and external tibial rotation. The results of this study indicate that PCL deficiency not only changed tibial translation, but also tibial rotation. Therefore, only evaluating the tibial translation in the anteroposterior direction may not completely describe the effect of PCL deficiency on knee joint function. Furthermore, the increased external tibial rotations were further hypothesized to cause elevated patello‐femoral joint contact pressures. These data may help explain the biomechanical factors causing long‐term degenerative changes of the knee after PCL injury. By fully understanding the etiology of these changes, it may be possible to develop an optimal surgical treatment for PCL injury that is aimed at minimizing the long‐term arthritic changes in the knee joint. © 2002 Orthopaedic Research Society. Published by Elsevier Science Ltd. All rights reserved.
Expression of AMPA/kainate receptors during development of chick embryo retina cells: in vitro versus in vivo studies
Authors: Cristóvão Armando J. , Oliveira Catarina R. , Carvalho Caetana M. 
Published: October 2002

AbstractThe activity and the subunit expression of α‐amino‐3‐hydroxy‐5‐methylisoxazole‐4‐propionate (AMPA)/kainate ionotropic glutamate receptors were studied in retina cells developing in chick embryos and in retina cells cultured as retinospheroids, at the same stages of development. In the retinospheroids, the activity of the AMPA/kainate receptors was monitored by following the changes in the intracellular free calcium concentration ([Ca2+]i), in response to AMPA, kainate or to l‐glutamate, and the expression of the receptor subunits GluR1, GluR2/3, GluR4 and GluR6/7 was determined in the retinospheroids and in chick retinas by immunodetection using polyclonal antibodies. The changes in [Ca2+]i in response to 400 μM kainate increased from 5 h in vitro to 3 days, and remained constant until day 14, whereas the [Ca2+]i in response to 500 μM l‐glutamate or 400 μM AMPA increased from 5 h in vitro to 3 days, and thereafter decreased slightly until day 14. The [Ca2+]i responses to kainate are mainly due to AMPA receptor stimulation, since the signals were abolished by LY303070, the AMPA receptor antagonist, and were not affected by MK‐801, the NMDA receptor antagonist. In retinospheroids, the levels of expression of GluR1 subunit increased from 5 h in vitro until day 7, then decreased until day 14. The levels of expression of GluR2/3 and GluR4 subunits increased from 5 h in vitro until day 10, and remained constant until day 14. The levels of kainate receptor subunits GluR6/7 increased from 5 h in vitro until day 3, and thereafter decreased slightly until day 14. In the retinas, the expression of GluR1 and GluR6/7 subunits increased from day 8 until day 15, and then decreased until day 22 (post‐natal 1). The subunits GluR2/3 and GluR4 increased from day 8 until day 18, and remained constant until day 22. The results suggest that AMPA/kainate receptors are expressed at early embryonic stages, although at low levels and before synapse formation (E12). However, the AMPA receptors are not completely functional at the first stage studied since they do not respond to the agonist AMPA. Also, the patterns of AMPA/kainate receptor subunit expression in retinospheroids of chick embryo retina cells cultured in vitro and in retina cells developing in the embryo (in vivo) were similar, indicating that the AMPA/kainate receptor subunits expression in these primary cultures mimics their expression in the developing chick retina.
Hospitalization for congestive heart failure: is it still a cardiology business?
Authors: Grigioni Francesco , Carinci Valeria , Favero Luca , Reggiani Letizia Bacchi , Magnani Gaia , Potena Luciano , Barbieri Alessandra , Magelli Carlo , Branzi Angelo , Magnani Bruno 
Published: October 2002

AbstractBackground:Hospital management of CHF and predictors of hospital mortality remain unclear.Methods:To address these issues, we analyzed the hospital admissions for CHF during 1996 in a large university hospital. Patients discharged with the principal diagnosis of CHF were considered eligible for the study.Results:Among the 1511 patients (3% of all discharges) who satisfied the inclusion criteria, 75% were treated in general medicine departments (GMD) and 22% in cardiology units (CU). Patients admitted to GMD were older than those treated in CU (79±10 vs. 68±15 years, P<0.001), included a higher proportion of females (56% vs. 37%, P<0.001), and presented a higher rate of hospital mortality (13% vs. 4%, P<0.001). The overall mean length of stay was 11±9 days. At multivariate analysis, length of stay was not associated with the department (i.e. GMD/CU) (P‐0.273).Conclusions:CHF is a common lethal condition often requiring treatment in GMD. Length of stay appears to depend more on patients' characteristics than on differences in practice between GMD and CU. Patients admitted to GMD present higher rates of comorbidity and hospital mortality. Strategies are urgently needed to improve hospital management of CHF.
Assessing exercise capacity, quality of life and haemodynamics in heart failure: do the tests tell us the same thing?
Authors: Houghton Andrew R. , Harrison Maxine , Cowley Alan J. , Hampton John R. 
Published: October 2002

AbstractBackground:The objective measurement of exercise tolerance is an important component of heart failure trials. The use of laboratory‐based treadmill exercise testing has attracted criticism, however, as being unrepresentative of patients’ true capabilities.Aim:To examine the relationships between tests of exercise capacity, quality of life and haemodynamics in patients with stable symptomatic heart failure.Methods:Thirty‐six patients with mild–moderate chronic heart failure were studied. Exercise capacity was assessed in the laboratory by maximal treadmill tests and self‐paced corridor walk tests, and in the patients’ homes by hip‐borne pedometers. Quality of life was assessed by a disease‐specific questionnaire. Cardiac output and limb blood flow were measured by non‐invasive techniques.Results:Customary activity as assessed by pedometer scores correlated with quality of life questionnaire scores (rS‐0.47, P‐0.04), and both variables correlated with limb (calf) blood flow (pedometer scores: rS‐0.39, P‐0.03; quality of life scores: rS‐0.50, P‐0.04). The laboratory‐based maximal treadmill test correlated with the self‐paced corridor walk test, but neither of these tests correlated with pedometer scores, quality of life or haemodynamics.Conclusions:Different methods of assessing exercise capacity do not appear to give comparable results and bear different relationships to haemodynamic variables and quality of life. Pedometer scores of customary activity may better reflect patients’ quality of life and appear to be more closely related to limb blood flow than the maximal treadmill exercise test or the corridor walk test. The sole use of laboratory‐based exercise tests in therapeutic trials may give a misleading assessment of treatment efficacy in heart failure patients.
Circulating cardiac autoantibodies in dilated cardiomyopathy and myocarditis: pathogenetic and clinical significance
Authors: Caforio Alida L.P. , Mahon Niall J. , Tona Francesco , McKenna William J. 
Published: October 2002

AbstractDilated cardiomyopathy (DCM) is a relevant cause of heart failure and a common indication for heart transplantation. It may be idiopathic, familial/genetic, viral, autoimmune or immune‐mediated associated with a viral infection. Myocarditis is an inflammatory disease of the myocardium; it may be idiopathic, infectious or autoimmune and may heal or lead to DCM. Thus, in a patient subset, myocarditis and DCM are thought to represent the acute and chronic stages of an organ‐specific autoimmune disease of the myocardium. In keeping with this hypothesis, autoimmune features in patients with myocarditis/DCM include: familial aggregation; a weak association with HLA‐DR4; abnormal expression of HLA class II on cardiac endothelium on endomyocardial biopsy; and detection of organ‐ and disease‐specific cardiac autoantibodies of the IgG class in the sera of affected patients and symptom‐free relatives. The cardiac autoantibodies detected by immunofluorescence are directed against multiple antigens. Two of these, first identified using immunoblotting and confirmed by ELISA, are the atrial‐specific α‐ and the ventricular and skeletal muscle β‐heavy chain isoform. The α‐myosin isoform fulfils the expected criteria for organ‐specific autoimmunity, in that immunization with cardiac, but not skeletal myosin reproduces, in susceptible mouse strains, the human disease phenotype of myocarditis/DCM; in addition, α‐myosin is entirely cardiac‐specific. Additional antigenic targets of heart‐reactive autoantibodies include unknown sarcolemmal proteins, mitochondrial enzymes, β‐adrenergic and muscarinic receptors. For some of these antibodies, there is in vitro evidence for a functional role. The organ‐specific cardiac autoantibodies detected by immunofluorescence in symptom‐free relatives were associated with echocardiographic features suggestive of early disease. Mid‐term follow‐up suggests that these antibodies are predictive markers of progression to DCM among symptom‐free relatives with or without abnormal echocardiographic findings.
Cardiac resynchronization therapy in advanced heart failure the multicenter InSync clinical study☆
Authors: Gras Daniel , Leclercq Christophe , Tang Anthony S.L. , Bucknall Cliff , Luttikhuis Henk Oude , Kirstein‐Pedersen Anders 
Published: October 2002

AbstractBackground:recent short‐term observations have shown an improvement in cardiac function and heart failure symptoms from atrio‐biventricular pacing. This study was designed to assess the safety and feasibility of an atrio‐biventricular transvenous pacing system, and examine the long‐term effects of cardiac resynchronization in patients with advanced heart failure and ventricular conduction abnormalities.Methods and results:between August, 1997 and November, 1998, 103 patients received a cardiac resynchronization system (CRS) consisting of a pulse generator interfaced with an atrio‐biventricular lead system, including a lead designed for left ventricular (LV) pacing via cardiac veins. Baseline evaluation included 12‐lead electrocardiogram, estimation of New York Heart Association (NYHA) functional class, assessment of quality of life (QOL), and distance covered during a 6‐min walk (6‐MW). Detailed echocardiographic data were also collected in a subset of 46 patients. Measurements were repeated in all surviving patients at 1, 3, 6 and 12 months after implantation of the CRS. A single, self‐limiting procedure‐related complication occurred. Over a follow‐up of 12 months, 21 patients died. The 12‐month actuarial survival was 78% (CI 70–87%). Nine surviving patients were withdrawn from the study during long‐term follow‐up for miscellaneous reasons. At each point of follow‐up, a significant shortening of QRS duration was measured. In addition, significant improvements were observed in mean NYHA functional class, 6‐MW and QOL score. In the 46 patients with complete echocardiographic data, LV ejection fraction increased from 21.7±6.4% at baseline to 26.1±9.0% at last follow‐up (P‐0.006), LV end diastolic dimension decreased from 72.7±9.2 to 71.6±9.1 mm (P‐0.233), interventricular mechanical delay decreased from 27.5±32.1 to 20.3±25.5 ms (P‐0.243), mitral regurgitation apical four‐chamber area decreased from 7.66±5.5 to 6.69±5.9 cm2 (P‐0.197), and left ventricular filling time increased from 363±127 to 408±111 ms (P‐0.002).Conclusions:long‐term cardiac resynchronization can be safely and reliably achieved by transvenous atrial synchronized right and left ventricular pacing. These changes were accompanied by clinically relevant improvements in functional status and QOL, as well as a measurable increase in LV performance. The outcome of randomised controlled trials is awaited.
Diagnosing diastolic heart failure
Authors: van Kraaij D.J.W. , van Pol P.E.J. , Ruiters A.W. , de Swart J.B.R.M. , Lips D.J. , Lencer N. , Doevendans P.A.F.M. 
Published: October 2002

AbstractBackgroundincreasing evidence supports the existence of left ventricular diastolic dysfunction as an important cause of congestive heart failure, present in up to 40% of heart failure patients.Aimto review the pathophysiology of LV diastolic dysfunction and diastolic heart failure and the currently available methods to diagnose these disorders.Resultsfor diagnosing LV diastolic dysfunction, invasive hemodynamic measurements are the gold standard. Additional exercise testing with assessment of LV volumes and pressures may be of help in detecting exercise‐induced elevation of filling pressures because of diastolic dysfunction. However, echocardiography is obtained more easily, and will remain the most often used method for diagnosing diastolic heart failure in the coming years. MRI may provide noninvasive determination of LV three‐dimensional motion during diastole, but data on correlation of MRI data with clinical findings are scant, and possibilities for widespread application are limited at this moment.Conclusionsin the forthcoming years, optimal diagnostic and therapeutic strategies for patients with primary diastolic heart failure have to be developed. Therefore, future heart failure trials should incorporate patients with diastolic heart failure, describing precise details of LV systolic and diastolic function in their study populations.
[123I]‐phenylpentadecanoic acid uptake in patients with dilated cardiomyopathy
Authors: Miche Eckart , Radzewitz Andrea , Notohamiprodjo Gunawan , Baller Detlev , Kloppe Axel , Eckert Siegfried , Gleichmann Ulrich 
Published: October 2002

AbstractBackgroundThe rate constant for global fatty acid influx (k1) was studied in 12 male patients with dilated cardiomyopathy (DCM). Method: 10 normal subjects served as controls. 201‐Thallium (201TI) and [123I]‐phenyl‐pentadecanoic acid (IPPA) were administered during bicycle exercise under fasting conditions.ResultsAll patients showed non‐homogeneous tracer uptake defects for 201TI and IPPA. k1 was significantly higher in DCM patients than controls. k1 showed significant inverse correlation between cardiac index, left‐ventricular ejection fraction, left‐ventricular enddiastolic pressure and echocardiographic left‐ventricular ejection fraction.ConclusionWe presume that an increased regional rate constant of IPPA influx into the myocardial tissue in patients with DCM reflects a compensatory mechanism of altered myocardium.
Study on biodegradable microspheres containing recombinant interferon-α-2a
Authors: Zhou Shaobing , Deng Xianmo , He Shuiying , Li Xiaohong , Jia Wenxiang , Wei Dapeng , Zhang Zairong , Ma Jihui 
Published: October 2002

Abstract
In this work, a new microsphere delivery system comprising calcium alginate microcores surrounded by a biodegradable poly-dl-lactide-poly(ethylene glycol) (PELA) coat was designed to improve the loading efficiency and stability of peptide drugs. Recombinant interferon (IFN)-α-2a, used as a model peptide drug, was efficiently entrapped within the alginate microcores using a high-speed stirrer and then microencapsulated into PELA copolymer using a water-in-oil-in-water solvent extraction method. Microspheres were characterized in terms of morphology, size and distribution, encapsulation efficiency, IFN biological activity retention and in-vitro peptide release. The IFN potency test showed that IFN entrapped in the core-coated microspheres could retain its biological activity during the encapsulation and release procedure. The release profiles were determined by the measurement of peptide presenting in the release medium at various intervals. The IFN potency, calculated by the Wish cells/vesicular stomatitis virus system, was used to determine IFN biological activity. The results showed that the core-coated microspheres could stabilize IFN in the PELA matrix. We compared the new delivery system with conventional microsphere delivery systems based on biodegradable poly-dl-lactide and poly-dl-lactide-poly(ethylene glycol). The core-coated microspheres had the highest amount of entrapment, encapsulation efficiency and biological activity retention. The extent of burst release (14%) from the core-coated microspheres in the initial protein release was much lower than the 31% burst release from the conventional microspheres. In conclusion, this work presents a new approach for water-soluble macromolecular drugs delivery (e.g. protein, peptide drugs, vaccines).
New bioreactor‐coupled rapid stopped‐flow sampling technique for measurements of metabolite dynamics on a subsecond time scale
Authors: Buziol Stefan , Bashir Imtiaz , Baumeister Anja , Claaßen Wolfgang , Noisommit‐Rizzi Naruemol , Mailinger Werner , Reuss Matthias 
Published: October 2002

AbstractKnowledge of concentrations of intracellular metabolites is important for quantitative analysis of metabolic networks. As far as the very fast response of intracellular metabolites in the millisecond range is concerned, the frequently used pulse technique shows an inherent limitation. The time span between the disturbance and the first sample is constrained by the time necessary to obtain a homogeneous distribution of the pertubation within the bioreactor. For determination of rapid changes, a novel sampling technique based on the stopped‐flow method has been developed. A continuous stream of biosuspension leaving the bioreactor is being mixed with a glucose solution in a turbulent mixing chamber. Through computer‐aided activation of sequentially positioned three‐way valves, different residence times and thus reaction times can be verified. The application of this new sampling method is illustrated with examples including measurements of adenine nucleotides and glucose‐6‐phosphate in Saccharomyces cerevisiae as well as measurements related to the PTS system in Escherichia coli. © 2002 Wiley Periodicals, Inc. Biotechnol Bioeng 80: 632–636, 2002.