bluuebunny/crossref_metadata_2025 huggingface dataset:
Experimental assessment of precision and accuracy of radiostereometric analysis for the determination of polyethylene wear in a total hip replacement model
Authors: Bragdon Charles R. , Malchau Henrik , Yuan Xunhua , Perinchief Rebecca , Kärrholm Johan , Börlin Niclas , Estok Daniel M. , Harris William H.
Published: October 2002

The purpose of this study was to develop and test a phantom model based on actual total hip replacement (THR) components to simulate the true penetration of the femoral head resulting from polyethylene wear. This model was used to study both the accuracy and the precision of radiostereometric analysis, RSA, in measuring wear. We also used this model to evaluate optimum tantalum bead configuration for this particular cup design when used in a clinical setting.

A physical model of a total hip replacement (a phantom) was constructed which could simulate progressive, three‐dimensional (3‐D) penetration of the femoral head into the polyethylene component of a THR. Using a coordinate measuring machine (CMM) the positioning of the femoral head using the phantom was measured to be accurate to within 7 μm. The accuracy and precision of an RSA analysis system was determined from five repeat examinations of the phantom using various experimental set‐ups of the phantom. The accuracy of the radiostereometric analysis, in this optimal experimental set‐up studied was 33 μm for the medial direction, 22 μm for the superior direction, 86 μm for the posterior direction and 55 μm for the resultant 3‐D vector length. The corresponding precision at the 95% confidence interval of the test results for repositioning the phantom five times, measured 8.4 μm for the medial direction, 5.5 μm for the superior direction, 16.0 μm for the posterior direction, and 13.5 μm for the resultant 3‐D vector length. This in vitro model is proposed as a useful tool for developing a standard for the evaluation of radiostereometric and other radiographic methods used to measure in vivo wear. © 2002 Orthopaedic Research Society. Published by Elsevier Science Ltd. All rights reserved.
Cell repopulation in vascularized bone grafts
Authors: Muramatsu Keiichi , Bishop Allen T.
Published: October 2002

Following 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

Aseptic 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

The 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

The 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.
Dangerous collusion: corruption as a collective venture in contemporary China
Authors: Gong Ting
Published: October 2002

Echoing changing social environments, corruption has grown in sophistication and complexity. This paper focuses on the phenomenon of collective corruption. Collective corruption, a distinctive form of social interaction among people dominated by individual calculations and unorganized interests, takes place when collaboration becomes a powerful, necessary weapon in pursuing private gains. The danger of collusion in corrupt ventures is that as corruption gets well planned and skillfully coordinated in its collective form, it may become less forthright and therefore more difficult to detect, or more overt and increasingly legitimized as an appropriate form of economic intercourse.
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

Background:

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

Background:

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

Dilated 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

Background:

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

Background

increasing 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.

Aim

to review the pathophysiology of LV diastolic dysfunction and diastolic heart failure and the currently available methods to diagnose these disorders.

Results

for 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.

Conclusions

in 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

Background

The 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.

Results

All 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.

Conclusion

We 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.
A Microlevel Analysis of Residential Context and Travel Time
Authors: Schwanen Tim , Dijst Martin , Dieleman Frans M
Published: October 2002

The literature on the association between residential context and travel concentrates on distance traveled and modal choice, as these variables are the most important from an environmental perspective. Travel time has received less attention—an unfortunate oversight in our view, as people's travel decisions are determined by time rather than by distance. By using data from the 1998 Netherlands National Travel Survey, we have considered travel time associated with trip purpose and transport mode, and have shown that sociodemographic factors and residential context influence daily travel time. Gender, number of workers in the household, age, and education all have a significant impact on travel time. The effects of car ownership and household income are only indirect, operating through mode choice and activity participation. Travel time for car drivers tends to rise with the degree of urbanisation of the residential environment. Further, in the polycentric metropolitan region of the Randstad, travel times by car are greater than in the monocentric regions of the country. It is also shown that in the Netherlands cycling and walking are still important travel modes, especially for shopping purposes. These results may be attributed to the long history of urbanisation and to planning policy in the Netherlands.
The Police Act and the Recruitment of Offenders: Towards the Limits of Social Exclusion?
Authors: Fletcher Del Roy
Published: October 2002

The social exclusion agenda has been enthusastically embraced by policymakers across Europe. A key feature of this agenda is the emphasis on paid work as a mechanism of social inclusion. However, the UK government is about to implement the Police Act (1997) which will increase the access of employers to the criminal records of job applicants. The author investigates how employers currently respond to job applications from offenders, and examines the likely impact of this new legislation on their recruitment. The key findings are that the Police Act will heighten discrimination against offenders, undermining the policy focus on combating social exclusion. This contradiction reflects the increasingly punitive response of successive UK governments to those committing criminal acts, and the narrow way in which social exclusion has been defined.
Danger Ahead? The Impact of Fear of Crime on People's Recreational Use of Nonmotorised Shared-Use Routes
Authors: Ravenscroft Neil , Uzzell David , Leach Rachel
Published: October 2002

In this paper we discuss the incidence of actual and perceived victimisation in people's recreational use of nonmotorised shared-use routes. Using the findings from eight focus groups, we show that, despite encountering very few conflictual situations when on shared-use routes, the fear of accidents and assaults has a significant impact on some people in some environments. The findings lend support to broader theorisations about people's insecurity when outside the home, where fear is an increasingly systemic reaction to the ways in which understandings of the public domain are shifting.
Insulin receptor substrate-2 maintains predominance of anabolic function over catabolic function of osteoblasts
Authors: Akune Toru , Ogata Naoshi , Hoshi Kazuto , Kubota Naoto , Terauchi Yasuo , Tobe Kazuyuki , Takagi Hideko , Azuma Yoshiaki , Kadowaki Takashi , Nakamura Kozo , Kawaguchi Hiroshi
Published: October 2002

Insulin receptor substrates (IRS-1 and IRS-2) are essential for intracellular signaling by insulin and insulin-like growth factor-I (IGF-I), anabolic regulators of bone metabolism. Although mice lacking the IRS-2 gene (IRS-2−/− mice) developed normally, they exhibited osteopenia with decreased bone formation and increased bone resorption. Cultured IRS-2−/− osteoblasts showed reduced differentiation and matrix synthesis compared with wild-type osteoblasts. However, they showed increased receptor activator of nuclear factor κB ligand (RANKL) expression and osteoclastogenesis in the coculture with bone marrow cells, which were restored by reintroduction of IRS-2 using an adenovirus vector. Although IRS-2 was expressed and phosphorylated by insulin and IGF-I in both osteoblasts and osteoclastic cells, cultures in the absence of osteoblasts revealed that intrinsic IRS-2 signaling in osteoclastic cells was not important for their differentiation, function, or survival. It is concluded that IRS-2 deficiency in osteoblasts causes osteopenia through impaired anabolic function and enhanced supporting ability of osteoclastogenesis. We propose that IRS-2 is needed to maintain the predominance of bone formation over bone resorption, whereas IRS-1 maintains bone turnover, as we previously reported; the integration of these two signalings causes a potent bone anabolic action by insulin and IGF-I.
MAL2, a novel raft protein of the MAL family, is an essential component of the machinery for transcytosis in hepatoma HepG2 cells
Authors: de Marco María C. , Martín-Belmonte Fernando , Kremer Leonor , Albar Juan P. , Correas Isabel , Vaerman Jean P. , Marazuela Mónica , Byrne Jennifer A. , Alonso Miguel A.
Published: October 2002

Transcytosis is used alone (e.g., hepatoma HepG2 cells) or in combination with a direct pathway from the Golgi (e.g., epithelial MDCK cells) as an indirect route for targeting proteins to the apical surface. The raft-associated MAL protein is an essential element of the machinery for the direct route in MDCK cells. Herein, we present the functional characterization of MAL2, a member of the MAL protein family, in polarized HepG2 cells. MAL2 resided selectively in rafts and is predominantly distributed in a compartment localized beneath the subapical F-actin cytoskeleton. MAL2 greatly colocalized in subapical endosome structures with transcytosing molecules en route to the apical surface. Depletion of endogenous MAL2 drastically blocked transcytotic transport of exogenous polymeric immunoglobulin receptor and endogenous glycosylphosphatidylinositol-anchored protein CD59 to the apical membrane. MAL2 depletion did not affect the internalization of these molecules but produced their accumulation in perinuclear endosome elements that were accessible to transferrin. Normal transcytosis persisted in cells that expressed exogenous MAL2 designed to resist the depletion treatment. MAL2 is therefore essential for transcytosis in HepG2 cells.
The state of ISO 9000 certification: a study of Swedish organizations
Authors: Poksinska Bozena , Jörn Dahlgaard Jens , Antoni Marc
Published: October 2002

It seems today to be an indisputable fact that ISO 9000 is a powerful instrument, which cannot be disregarded. It is, far and away, the most influential initiative that grew from the quality movement of the late 1980s. This paper contains an evaluation of results from a survey on ISO 9000 certified companies and aims to present some aspects of the current state of the standard in Swedish industry. This study is focused on motives for implementation, perceived benefits and key implementation factors. The predominant reasons identified for seeking certification were the desire to improve corporate image and quality. Like many previous studies this study underlines the need for management commitment and participation. The very important conclusion drawn from this survey is that the motivation for certification may influence the performance of ISO 9000. The overall benefits which the companies gain from the standard showed dependence on the motivation which initiated the drive for the certification.
Quality management in construction: an innovative advance using project alliancing in Australia
Authors: Walker Derek H.T. , Keniger Michael
Published: October 2002

This paper presents an account of the quality management system designed and adopted using a project alliance approach on the National Museum of Australia project. We discuss the integration of the selection criteria and performance measures and how these were used to provided a risk and reward structure that provided the incentive for a high level of achievement of the projects’ goals. Interestingly, the organisational structure of the project alliance provided a cross‐team relationship outcome that sealed the quality culture observed on this project. This culture drove high levels of quality and was also observed to appeal to intrinsic motivation to deliver best‐for‐project outcomes.
A survey of emerging technologies for pricing new‐to‐the‐world products
Authors: Bergstein Heather , Estelami Hooman
Published: October 2002

New‐to‐the‐world products are innovations that represent leapfrogging advancements in product design, which often result in significant gains in consumer utility. Such new products are critical not only because of their ability to become a means for market share gain and revenue growth, but also because they often change the competitive landscape of the markets they are launched in. A fundamental concern in developing new‐to‐the‐world products is the appropriate pricing of these products. In this paper, we will first review the traditional methods used in determining the prices of new‐to‐the‐world products. We will then profile emerging technologies that have found extensive use in recent years and are helping accelerate the pricing process of new‐to‐the‐world products. The paper will conclude with a discussion of the implications of these emerging technologies on the practice of pricing.
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

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

Knowledge 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.
Reduction kinetics of Fe(III), Co(III), U(VI), Cr(VI), and Tc(VII) in cultures of dissimilatory metal‐reducing bacteria
Authors: Liu Chongxuan , Gorby Yuri A. , Zachara John M. , Fredrickson Jim K. , Brown Christopher F.
Published: October 2002

The reduction kinetics of Fe(III)citrate, Fe(III)NTA, Co(III)EDTA−, U(VI)O22+, Cr(VI)O42−, and Tc(VII)O4− were studied in cultures of dissimilatory metal reducing bacteria (DMRB): Shewanella alga strain BrY, Shewanella putrefaciens strain CN32, Shewanella oneidensis strain MR‐1, and Geobacter metallireducens strain GS‐15. Reduction rates were metal specific with the following rate trend: Fe(III)citrate ≥ Fe(III)NTA > Co(III)EDTA− > UO22+ > CrO42− > TcO4−, except for CrO42− when H2 was used as electron donor. The metal reduction rates were also electron donor dependent with faster rates observed for H2 than lactate− for all Shewanella species despite higher initial lactate (10 mM) than H2 (0.48 mM). The bioreduction of CrO42− was anomalously slower compared to the other metals with H2 as an electron donor relative to lactate and reduction ceased before all the CrO42− had been reduced. Transmission electron microscopic (TEM) and energy‐dispersive spectroscopic (EDS) analyses performed on selected solids at experiment termination found precipitates of reduced U and Tc in association with the outer cell membrane and in the periplasm of the bacteria. The kinetic rates of metal reduction were correlated with the precipitation of reduced metal phases and their causal relationship discussed. The experimental rate data were well described by a Monod kinetic expression with respect to the electron acceptor for all metals except CrO42−, for which the Monod model had to be modified to account for incomplete reduction. However, the Monod models became statistically over‐parametrized, resulting in large uncertainties of their parameters. A first‐order approximation to the Monod model also effectively described the experimental results, but the rate coefficients exhibited far less uncertainty. The more precise rate coefficients of the first‐order model provided a better means than the Monod parameters, to quantitatively compare the reduction rates between metals, electron donors, and DMRB species. © 2002 Wiley Periodicals, Inc. Biotechnol Bioeng 80: 637–649, 2002.
Enantiomeric separation of diuretics on a novel pirkle‐type chiral stationary phase
Authors: Vercauteren Ann , Weken Guido Van der , Vankeirsbilck Tineke , Aboul‐Enein Hassan Y. , Baeyens Willy R. G.
Published: October 2002

A newly developed Pirkle‐type straight chiral stationary phase (CSP), based on the 3,5‐dinitrobenzoyl derivative of 1,2 diphenylethylene‐diamine and known as ULMO, has been successfully applied to the direct resolution of the enantiomers of several diuretics by liquid chromatography. In this study, the effect of changes in the mobile phase and the intrinsic stereoselective properties of this CSP towards a specific racemate are determined experimentally. A mobile phase consisting of n‐hexane and 2‐propanol appears most appropriate for the chiral separation of the tested diuretics on the ULMO‐column. Copyright © 2002 John Wiley & Sons, Ltd.
A new method for determination of buformin in plasma and urine by ion‐paired reversed‐phase HPLC with ultraviolet detection
Authors: Yamamoto Takehito , Kusama Makiko , Matsuno Kumi , Sugiyama Erika , Yamada Yasuhiko , Iga Tatsuji
Published: October 2002

Buformin is a widely used as an antidiabetic agent but its renal excretion is still controversial. A new HPLC method with ultraviolet (UV) detection for the determination of buformin in plasma and urine has been developed. After protein precipitation or dilution, buformin and internal standard phenformin were resolved on an octadecyl silica column and detected by UV detection at 233 nm. Intra‐ and inter‐day coefficients of variation were <9%. The limit of quantification was around 0.05 µg/ml for plasma and 2.5 µg/ml for urine. Copyright © 2002 John Wiley & Sons, Ltd.
Investigation of propofol renal elimination by HPLC using supported liquid membrane procedure for sample preparation
Authors: Dawidowicz Andrzej L. , Kalityński Rafał , Trocewicz Jerzy , Nestorowicz Andrzej , Fijałkowska Anna , Trela‐Stachurska Katarzyna
Published: October 2002

One of the least explored subjects in the research on the metabolism of a widely used anaesthetic, propofol, is its excretion in an unchanged form. According to literature, the estimated percentage of applied propofol eliminated intact via kidneys is lower than 0.3%. The present study shows the amount of propofol excreted in an unchanged form with urine collected during the first 48 h after anaesthesia in five patients undergoing elective intracranial procedures. The drug was concentrated and selectively isolated from urine samples by supported liquid membrane technique and determined by HPLC with fluorescence detection. The amount of unchanged propofol eliminated with urine was approximately (0.004 ± 0.002)% of the total applied dose. The obtained results may suggest that propofol in an unchanged form is not excreted by kidneys at all provided that all propofol determined in presented study originated from conjugates hydrolysis. Copyright © 2002 John Wiley & Sons, Ltd.
The alpha‐factor receptor C‐terminus is important for mating projection formation and orientation in Saccharomyces cerevisiae
Authors: Vallier Laura G. , Segall Jeffrey E. , Snyder Michael
Published: October 2002

Successful mating of MATa Saccharomyces cerevisiae cells is dependent on Ste2p, the α‐factor receptor. Besides receiving the pheromone signal and transducing it through the G‐protein coupled MAP kinase pathway, Ste2p is active in the establishment and orientation of the mating projection. We investigated the role of the carboxyl terminus of the receptor in mating projection formation and orientation using a spatial gradient assay. Cells carrying the ste2‐T326 mutation, truncating 105 of the 135 amino acids in the receptor tail including a motif necessary for its ligand‐mediated internalization, display slow onset of projection formation, abnormal shmoo morphology, and reduced ability to orient the mating projection toward a pheromone source. This reduction was due to the increased loss of mating projection orientation in a pheromone gradient. Cells with a mutated endocytosis motif were defective in reorientation in a pheromone gradient. ste2‐Δ296 cells, which carry a complete truncation of the Ste2p tail, exhibit a severe defect in projection formation, and those projections that do form are unable to orient in a pheromone gradient. These results suggest a complex role for the Ste2p carboxy‐terminal tail in the formation, orientation, and directional adjustment of the mating projection, and that endocytosis of the receptor is important for this process. In addition, mutations in RSR1/BUD1 and SPA2, genes necessary for budding polarity, exhibited little or no defect in formation or orientation of mating projections. We conclude that mating projection orientation depends upon the carboxyl terminus of the pheromone receptor and not the directional machinery used in budding. Cell Motil. Cytoskeleton 53:251–266, 2002. © 2002 Wiley‐Liss, Inc.
Rescue of a Chlamydomonas inner‐arm‐dynein‐deficient mutant by electroporation‐mediated delivery of recombinant p28 light chain
Authors: Hayashi Masahito , Yanagisawa Haru‐aki , Hirono Masafumi , Kamiya Ritsu
Published: October 2002

We have recently shown that rabbit actin can be introduced by electroporation into the Chlamydomonas ida5 mutant lacking conventional actin and rescue its mutant phenotype [Hayashi et al., 2001: Cell Motil. Cytoskeleton 49:146–153]. In this study, we explored the possibility of using electroporation for functional assay of a recombinant protein. The p28 light chain of inner‐arm dyneins was expressed in Escherichia coli, purified to homogeneity, and introduced by electroporation into a non‐motile mutant ida4oda6 that lacks it. Because this protein was insoluble in the low ionic strength solution used in the previous study, electroporation was performed at physiological ionic strength in the presence of Ca2+. Most cells shed their flagella after electroporation. Reflagellation took place within 3 h and up to 30% of the cells became motile, indicating that the introduced p28 retained its functional activity. Fluorescently‐labeled p28 was equally effective; in this case fluorescence was observed along the flagella. The presence of Ca2+ and deflagellation appeared to be important for efficient protein delivery, because a triple mutant with the fa1 mutation deficient in the flagellar shedding mechanism recovered motility only very poorly. Similar results were obtained with other combinations of recombinant proteins and mutants. This study thus demonstrates the feasibility of using electroporation for activity assays of recombinant proteins. Cell Motil. Cytoskeleton 53:273–280, 2002. © 2002 Wiley‐Liss, Inc.
Transient expression of the t‐isoform of plastins/fimbrin in the stereocilia of developing auditory hair cells
Authors: Daudet Nicolas , Lebart Marie‐Christine
Published: October 2002

The transduction of auditory signals by cochlear hair cells depends upon the integrity of hair cell stereociliary bundles. Stereocilia contain a central core of actin filaments, cross‐linked by actin bundling proteins. In the cochlea, the two proteins described to date as responsible for the spatial arrangement of actin filaments in sterocilia are fimbrin and the recently discovered espin. Fimbrin (the chick homolog of human I‐plastin) belongs to the plastins/fimbrin family that includes two additional isoforms of plastins, T‐ and L‐plastin. In the present study, we used isoform specific antibodies to investigate the presence of the T‐ and L‐isoforms of plastin/fimbrin in the adult and developing rat cochlea. We found that T‐plastin, but not L‐plastin, is expressed in the rat cochlea. During postnatal development of the rat organ of Corti, T‐plastin can be detected in the core of stereocilia from early stages of hair cell differentiation, and its expression gradually increases in stereocilia as hair cells mature. However, as opposed to other actin‐binding proteins expressed in stereocilia, T‐plastin is absent from the stereocilia of mature hair cells. Such temporally restricted expression strengthens the idea of functional differences between plastins isoforms, and suggests that T‐plastin could have a specific role in stereocilia formation. Cell Motil. Cytoskeleton 53:326–336, 2002. © 2002 Wiley‐Liss, Inc.
Optimization of heat sink mass using the DYNAMIC‐Q numerical optimization method
Authors: Visser J. A. , de Kock D. J.
Published: October 2002

Heat sink designers have to balance a number of conflicting parameters to maximize the performance of a heat sink. This must be achieved within the given constraints of size or volume of the heat sink as well as the mass or material cost of the heat sink. This multi‐parameter problem lends itself naturally to optimization techniques. Traditionally, an experimental approach was used where different heat sink designs were constructed and their performance measured. This approach is both time consuming and costly. More recently, numerical CFD techniques have been used, but mostly on a trial‐and‐error basis, and is basically the numerical equivalent of the experimental approach. A better approach is to combine a semi‐empirical simulation program with mathematical optimization techniques. This paper describes the use of mathematical optimization techniques to minimize heat sink mass. The simulation uses the Qfin 2.1 code, while the optimization is carried out by means of the DYNAMIC‐Q method. This method is extremely robust and specifically designed to handle constrained problems where the objective and/or constraint functions are expensive to evaluate. The paper illustrates how the parameters considered influence the heat sink mass and how mathematical optimization techniques can be used by the heat sink designer to design compact heat sinks for different types of electronic enclosures. Copyright © 2002 John Wiley & Sons, Ltd.