bluuebunny/crossref_metadata_2025 huggingface dataset:
Topology determination and functional analysis of the Escherichia coli TatC protein
Authors: Gouffi Kamila , Santini Claire-Lise , Wu Long-Fei
Published: October 2002

The TatC protein is an essential component of the bacterial Tat system. By using alkaline phosphatase and β‐glucuronidase fusions we found that TatC contains four transmembrane helices. Three insertions of Ala‐Ser dipeptide at the cytoplasmic N‐ and C‐termini and in the cytoplasmic loop had no or only partial effect on the TatC function. In contrast, five of seven insertions in the two periplasmic loops abolished the Tat function. Four insertions analyzed had no effect on the stability of the altered TatC proteins or on membrane assembly of the TatA and TatB proteins. These data provide a novel base for more detailed studies of the mechanism of the Tat system.
Bone‐mass peak in multiparity and reduced risk of bone‐fractures in menopause
Authors: Cure‐Cure C , Cure‐Ramı́rez P , Terán E , López‐Jaramillo P
Published: October 2002

Objectives: Pregnancy has been proposed as a risk factor for the development of osteoporosis; however, the results are controversial. Women in Colombia are multiparous, and therefore they represent an ideal population for the investigation of the effect of parity on osteoporosis. Methods: The study included 1855 post‐menopausal Hispanic women from Barranquilla, Colombia who were referred to our osteoporosis clinic for a routine evaluation of their bone mineral status. Bone mineral density (BMD, g/cm2) was measured using dual energy X‐ray absorptiometry. Total body, femoral and lumbar areas were scanned. Results: BMD of total body, hip and legs (P<0.0001), Ward's area (P<0.002) and intertrochanteric area (P<0.003) was high in women with at least one delivery in comparison with nulliparous women. Total mineral and calcium body contents were also high in women after second delivery. A history of fractures was found in 22.9% (n=425) of the study women. The relative risk for bone‐fractures was high (O.R. 0.41; P<0.000002) in nulliparous women in comparison to multiparous women. In addition, osteopenia (O.R. 2.01; P=0.008) and osteoporosis (O.R. 3.99; P=0.0004) were most often present in nulliparous women in comparison to multiparous women. Conclusions: Pregnancies in this population appear to be a protective factor against development of osteoporosis. The increase in total mineral and calcium contents was related to the number of pregnancies, suggesting the existence of a bone mass peak during pregnancy.
Obstetric deaths in Bangladesh, 1996–1997
Authors: Rahman M.H. , Akhter H.H. , Khan Chowdhury M.‐E.‐E. , Yusuf H.R. , Rochat R.W.
Published: October 2002

Objectives: The purpose of this study was to measure and to describe obstetric deaths in Bangladesh. Methods: We reviewed hospital records and interviewed health workers in clinic sites and field workers who cared for pregnant women. Results: We obtained case reports of 28 998 deaths of women aged 10–50, of which 8562 (29.5%) were maternal deaths. Most (7086, 82.8%) of these deaths were due to obstetric causes. The most common causes of direct obstetric death were eclampsia (34.3%), hemorrhage (27.9%), and obstructed and/or prolonged labor (11.3%). National direct obstetric death rate was estimated to be 16.9 per 100 000 women. Conclusions: Efforts to reduce fertility in Bangladesh have led to an estimated 49% reduction in the maternal mortality rate per 1000 women during the past 18 years. Variations in maternal mortality suggest the need to develop local strategies to improve obstetric care.
Digital examination compared to trans‐perineal ultrasound for the evaluation of anal sphincter repair
Authors: Shobeiri S.A. , Nolan T.E. , Yordan‐Jovet R. , Echols K.T. , Chesson R.R.
Published: October 2002

Objective: To assess the adequacy of a third‐ or a fourth‐degree laceration repair by comparing digital and trans‐perineal ultrasound measurements. Method: During a 4‐year period, 34 subjects without prior history of anal sphincter injury or fecal incontinence underwent ultrasound measurements of external anal sphincter muscle diameter and perineal length, which were compared to measurements obtained by digital examination. Results: Pearson's correlation coefficients for comparing the digital external sphincter examination to trans‐perineal ultrasonography, and the digital perineal examination to trans‐perineal ultrasonography were 0.88 and 0.40, respectively. Patients (n=4/34) whose external sphincter was identified as less than 1 cm by digital examination were found to have an external sphincter diameter of less than 1 cm by trans‐perineal ultrasound. Conclusion: The digital perineum examination is a reliable method of measuring the external sphincter thickness and perineal body length immediately after primary repair.
Direction‐dependent resistance to flow in the endplate of the intervertebral disc: an ex vivo study
Authors: Ayotte D. C. , Ito K. , Tepic S.
Published: October 2002

A comparison of the higher hydrostatic pressure in the nucleus of the healthy intervertebral disc during daily loading with the relatively lower osmotic swelling pressure in the disc during rest suggests the existence of direction‐dependent flow resistance such that all of the fluid exuded from the disc during loading is recovered during rest. In this study, this direction‐dependent resistance was demonstrated for flows through the cartilage endplates and the underlying marrow contact channels in the bony endplates. Using an ex vivo sheep endplate model, the resistance ratio (Rout/Rin) for flow through the endplate was 39.0 ± 3.8 (mean ± S.E.). In addition, a path of fluid flow through the marrow contact holes was revealed using fluorescent staining. © 2001 Orthopaedic Research Society. Published by Elsevier Science Ltd. All rights reserved.
Involvement of BMP‐2 signaling in a cartilage cap in osteochondroma
Authors: Nakase Takanobu , Myoui Akira , Shimada Kozo , Kuriyama Kohji , Joyama Susumu , Miyaji Takahiro , Tomita Tetsuya , Yoshikawa Hideki
Published: October 2002

This study describes the distributions of bone morphogenetic protein (BMP)‐2 as well as mRNAs for BMP receptor type IB (BMPRIB), collagen types II (Col II) and III (Col III) in a growing “cartilage cap” of osteochondroma. In situ hybridization and immunohistochemical study were performed using histological sections obtained during surgery. BMP‐2 was detected in mesenchymal cells in the outer fibrous layer and chondrocytes in the inner cartilaginous matrix, positive for Col III and Col II, respectively. BMPRIB mRNA was distributed in chondrocytes. This is the first study to provide observational evidence of the involvement of BMP‐2 signaling in the pathogenesis of cartilage cap of osteochondroma, and suggests the role of BMP‐2 in the growth of cartilage cap in osteochondroma. © 2001 Orthopaedic Research Society. Published by Elsevier Science Ltd. All rights reserved.
Characterization of nucleus pulposus‐like tissue formed in vitro
Authors: Sun Yongliang , Hurtig Mark , Pilliar Robert M. , Grynpas Marc , Kandel Rita A.
Published: October 2002

In order to be able to study the metabolism of nucleus pulposus (NP) tissue, we developed a cell culture system that resulted in the formation of NP‐like tissue in vitro. NP cells were isolated from sheep lumbar spines and grown on filter inserts (Millicell CM®). Histological examination showed that the cells accumulated extracellular matrix and formed a continuous layer of NP‐like tissue. The accumulation of sulfated proteoglycans in the NP‐like tissue continued up to 10 weeks and this was paralleled by an increase in tissue thickness and dry weight. DNA content remained stable during the first 4 weeks but then decreased over time. The amount of DNA, glycosaminoglycan (GAG) and collagen per mg dry weight of the tissue generated after 10 weeks in culture were 1.25 ± 0.02, 301.6 ± 27.7 and 411 ± 65 μg, respectively, compared with 1.04 ± 0.08, 320.6 ± 21.2 and 399 ± 4.4 μg (mean ± SEM) for the in vivo tissue. There was no significant difference between in vitro and in vivo tissue. The cells in culture synthesized large proteoglycans (kav = 0.26 ± 0.03, mean ± S.D.) which were similar in size to those synthesized by cells in NP tissue in ex vivo culture (kav = 0.22 ± 0.02, mean ± S.D.) as determined by Sepharose CL‐2B column chromatography. The in vitro generated tissue contained type II collagen as demonstrated by sodium dodecyl sulfate‐polyacrylamide gel (SDS‐PAGE) and silver staining as well as Western blot analysis. NP cells grown on filters generate tissue similar in composition to the in vivo tissue, for the characteristics examined to date, and should be a suitable model to use to study NP metabolism and extracellular matrix turnover. © 2001 Orthopaedic Research Society. Published by Elsevier Science Ltd. All rights reserved.
The role of osteoclast differentiation in aseptic loosening
Authors: Greenfields Edward M. , Bi Yamming , Ragab Ashraf A. , Goldberg Victor M. , Van De Motter R. Renee
Published: October 2002

The major cause of orthopaedic implant loosening is thought to be accelerated osteoclastic bone resorption due to the action of cytokines produced in response to phagocytosis of implant‐derived wear particles. This accelerated osteoclastic bone resorption could be due to increases in any of the following processes: recruitment of osteoclast precursors to the local microenvironment, differentiation of precursors into mature multinucleated osteoclasts, activation of mature osteoclasts, and/or survival of osteoclasts. Our studies have focused on differentiation and survival to complement work by others who have focused on recruitment of precursors and activation. Taken together, our studies and those of other investigators provide strong evidence that increased recruitment of osteoclast precursors and their subsequent differentiation play major roles in wear particle‐induced osteolysis. In contrast, increased osteoclast activation and survival appear to play minor roles. These studies suggest that development of therapeutic interventions that reduce either recruitment or differentiation of osteoclast precursors would improve the performance of orthopaedic implants. © 2002 Orthopaedic Research Society. Published by Elsevier Science Ltd. All rights reserved.
A biodegradable composite scaffold for cell transplantation
Authors: Ameer G. A. , Mahmood T. A. , Langer R.
Published: October 2002

Cell transplantation is rapidly becoming a therapeutic option to treat disease and injury. However, standard techniques for cell seeding on non‐woven polymer meshes or within gels may not be suitable for immediate implantation or surgical manipulations of freshly isolated cells. Therefore, a biodegradable composite system was developed as a way to rapidly entrap cells within a support of predefined shape to potentially facilitate cell delivery into a target site (e.g. meniscal tears in the avascular zone). The composite construct consisted of freshly isolated cells, in this case pig chondrocytes, entrapped in a fibrin gel phase and dispersed throughout the void volume of a polyglycolic acid (PGA) non‐woven mesh. Composites were cultured for up to 4 weeks. In vitro degradation of fibrin gel was evaluated via gel‐entrapped urokinase. At 28 days in culture, glycosaminoglycan (GAG) content per cell in the composite scaffolds was 2.6 times that of the PGA‐only cell construct group and 88% that of native pig cartilage. Total collagen content per cell in the composite scaffolds was not significantly different from the PGA‐only cell construct group (P > 0.02) and represented 40% of the value determined for native cartilage. Varying the concentration of entrapped urokinase could effect controlled degradation of fibrin gel. © 2002 Orthopaedic Research Society. Published by Elsevier Science Ltd. All rights reserved.
Nitric oxide induces osteoblast apoptosis through the de novo synthesis of Bax protein
Authors: Chen Ruei‐Ming , Liu Hwa‐Chang , Lin Yi‐Ling , Jean Wen‐Chyi , Chen Jui‐Shui , Wang Jyh‐Horng
Published: October 2002

Nitric oxide (NO) plays a crucial role in the physiological and pathophysiological regulations of osteoblast functions. This study is designed to evaluate the toxic effects of NO released by sodium nitroprusside (SNP), an NO donor, on neonatal Wistar rat calvarial osteoblasts from the analyses of cell viability, alkaline phosphatase (ALP) activity, cell morphology, apoptotic cells, terminal deoxynucleotidyl transferase‐mediated dUTP nick end‐label (TUNEL) assay, DNA ladder, and immunocytochemistry and Western blot for proapoptotic Bax protein. SNP increased the levels of nitrite, an oxidative product of NO, in the culture medium of osteoblasts in concentration‐ and time‐dependent manners, and altered cell morphologies to round and shrinkage shapes. Administration of osteoblasts with SNP resulted in concentration‐ and time‐dependent decreases of cell viability and ALP activity. Analysis of apoptotic cells revealed that SNP increased the percentages of osteoblasts processing apoptosis. Analyses of TUNEL and DNA ladder showed that SNP caused DNA fragmentation. Pretreatment with cycloheximide, an inhibitor of protein synthesis, partially blocked SNP‐induced osteoblast apoptosis. Imunocytochemical and immunoblotting analyses revealed that SNP increased Bax protein in osteoblasts. This study suggests that SNP could increase the levels of NO in osteoblasts, and cause osteoblast apoptosis possibly through the de novo synthesis of proapoptotic Bax protein. © 2002 Orthopaedic Research Society. Published by Elsevier Science Ltd. All rights reserved.
Plantar impact causing midfoot fractures result in higher forces in Chopart's joint than in the ankle joint
Authors: Richter M. , Wippermann B. , Thermann H. , Schroeder G. , Otte D. , Troeger H. D. , Krettek C.
Published: October 2002

Purpose. Force effect (impact, extent of foot compartment deformation) and result (fracture pattern) for midfoot fractures in car occupants is known. An analysis of the processes in the foot was intended to improve car safety.

Materials and methods. Eleven fresh, unfrozen, unpreserved intact human cadavers (age: 36.8 (16–61) years, gender: male, race: Caucasian) were studied 24–72 h after death. In 3 cadavers (5 feet) the experimental design was established: entire cadaver fixed on a special tray in supine position, pendulum with bar impactor hitting the foot plantar to Lisfranc's joint. A custom‐made pressure sensor was inserted in the ankle (A), talonavicular (TN) and calcaneocuboid (CC) joints (resolution: 1 cm2, sampling rate: 500/s).

Results. Sixteen feet were measured; midfoot fractures were induced in 11 feet. The maximum pressure amounted to 1.22–2.55 MPa (2.04 ± 0.412) at 0.005–0.195 s (0.067 ± 0.059) after impact. The maximum pressure occurred in 8 (50%) cases in the ankle, in 7 (44%) of the TN and 1 (6%) of the CC joints. A comparison of the first 200 pressure samples after impact of all sensor fields resulted in higher forces in Chopart's joint than in the ankle (t‐test: p < 0.001). These force differences were higher in cases with midfoot fractures (mixed model analysis of variance: p = 0.003).

Conclusion. Due to considerable forces in Chopart's joint we recommend a modification of the actual crash test dummy lower extremity model with an additional load cell that detects forces in the longitudinal direction of the foot axis. © 2002 Orthopaedic Research Society. Published by Elsevier Science Ltd. All rights reserved.
The characterization of versican and its message in human articular cartilage and intervertebral disc
Authors: Sztrolovics Robert , Grover Judy , Cs‐Szabo Gabriella , Shi Shui‐Liang , Zhang Yiping , Mort John S. , Roughley Peter J.
Published: October 2002

Splicing variation of the versican message and size heterogeneity of the versican core protein were analyzed in human articular cartilage and intervertebral disc. Splicing variation of the message was studied by PCR analysis to detect the presence or absence of exons 7 and 8, which encode large chondroitin sulfate attachment regions. At all ages in normal cartilage from the third trimester fetus to the mature adult, the presence of the versican isoform possessing exon 8 but not exon 7 (V1) could be readily detected. The message isoforms possessing neither exon 7 nor 8 (V3) or both exons 7 and 8 (V0) were only detectable in the fetus, and the isoform possessing only exon 7 (V2) was never detected. In osteoarthritic cartilage and in adult intervertebral disc the versican message pattern was the same as that observed in the normal adult with only the isoform possessing exon 8 being detected. Core protein heterogeneity was studied by immunoblotting following enzymic removal of the glycosaminoglycan chains from the proteoglycan, using an antibody recognizing the globular G1 region of versican. All articular cartilage extracts from the fetus to the mature adult contained multiple core protein sizes of greater than 200 kDa. The adult cartilage extracts tended to have an increased proportion of the smaller sized core proteins and osteoarthritic cartilage possessed similar core protein sizes to the normal adult. In contrast, intervertebral disc at all post‐natal ages showed a greater range of size heterogeneity with a prominent component of about 50 kDa. The abundance of this component increased if the samples were treated with keratanase prior to analysis, suggesting that the G1 region of versican in disc can be substituted with keratan sulfate. The increased presence of versican in the disc relative to articular cartilage may suggest a more pronounced functional role for this proteoglycan, particularly in the nucleus pulposus. © 2002 Orthopaedic Research Society. Published by Elsevier Science Ltd. All rights reserved.
Photodynamic treatment has chondroprotective effects on articular cartilage
Authors: Sullivan Lawrence G. , Hasan Tayyaba , Wright Marianne , Mankin Henry J. , Towle Christine A.
Published: October 2002

Osteoarthritis (OA) is a disabling joint disease for which there is currently no cure. It is characterized by the destruction of articular cartilage. One strategy that is being explored for protecting the cartilage in OA is the administration of transforming growth factor‐β, which in vitro antagonizes cartilage degradation initiated by catabolic stimulants such as interleukin‐1 (IL‐1). The problems associated with selective delivery of the growth factor to chondrocytes, undesirable side‐effects on joint tissues, and short biological half‐life have led us to explore modalities aimed at activating transforming growth factor‐β that is stored in the cartilage as latent complexes. Photodynamic therapy is a two‐step protocol of tissue sensitization with a light‐activatable chemical called a photosensitizer followed at some interval by irradiation with the appropriate wavelength visible light. Biological effects are typically elicited through oxygen‐dependent photochemistry without heat generation. Transforming growth factor‐β1 can be activated by oxidative mechanism(s), prompting us to explore whether photodynamic technology can be harnessed to modulate cartilage metabolism. Disks of bovine articular cartilage were photosensitized by incubation with a chlorine6‐succinylated polylysine conjugate and irradiated with 1–2 J/cm2 red light (λmax = 671 nm). This two‐step regimen dramatically inhibited IL‐1‐stimulated proteoglycan degradation and concomitantly increased latent and active transforming growth factor‐β1 in culture medium. This research may lead to the development of minimally invasive photodynamic therapy in which light is delivered to locally activate a chondroprotective program in photosensitized cartilage in the context of OA. © 2002 Orthopaedic Research Society. Published by Elsevier Science Ltd. All rights reserved.
Development of a cellular model to study alternative splicing of type II collagen gene
Authors: Hatano H. , Sarkar G. , Bolander M. E.
Published: October 2002

To study regulation of alternative splicing of type II collagen (COL2) pre‐mRNA, we constructed a mouse COL2 “minigene” containing genomic sequences spanning exon 1 to exon 4 of COL2 downstream of a cytomegalovirus (CMV) promoter. This minigene was introduced into ATDC5 cells, which undergo chondrocytic differentiation when treated with insulin. Alternative splicing of the COL2 minigene was evaluated by comparing the expression of the two mRNAs transcribed from the minigene to the expression of alternatively spliced transcripts from the endogenous COL2 gene: This analysis suggested that regulation of alternative splicing of pre‐mRNAs from the minigene and the endogenous COL2 gene are accomplished by similar mechanisms. We conclude that the cloned genomic fragment contains key sequences necessary for alternative splicing of COL2 pre‐mRNA. This system provides a useful model to begin the process of identifying cis‐ and trans‐acting factors that carry out alternative splicing of COL2 pre‐mRNA during chondrocyte differentiation. © 2002 Orthopaedic Research Society. Published by Elsevier Science Ltd. All rights reserved.
The insertion site of the canine flexor digitorum profundus tendon heals slowly following injury and suture repair
Authors: Silva Matthew J. , Boyer Martin I. , Ditsios Konstantinos , Burns Meghan E. , Harwood Frederick L. , Amiel David , Gelberman Richard H.
Published: October 2002

Treatment of injuries of the flexor digitorum profundus (FDP) tendon insertion site has changed little during the past 50 years, in part because there are no reports describing flexor tendon insertion site healing. Our objective was to assess the effects of repair technique and post‐operative time on tendon–bone healing using a canine model of injury and repair. We transected 48 FDP tendons from 24 dogs at their insertions and repaired them using either a four‐ or eight‐strand suture technique. We assessed the mechanical properties of the repaired tendon–bone construct, tendon collagen biochemistry, and distal phalanx bone mineral density (BMD) at 0, 10, 21 and 42 days. Suture method had no significant effect on any outcome (p > 0.05). In particular, use of an eight‐strand double modified Kessler technique did not result in increased stiffness or strength compared to a four‐strand technique. With time, the repair site became stiffer, as demonstrated by a 230% increase in rigidity and a 50% decrease in strain from 0 to 42 days. However, from 0 to 42 days the ultimate force of the insertion site did not increase. This lack of increase in ultimate force was consistent with decreases in collagen content, non‐reducible crosslinks and distal phalanx BMD. Taken together, our results indicate that the canine FDP tendon heals slowly after it is injured at its insertion site and sutured onto the distal phalanx. While these findings may be limited to the particular repair method we used, they demonstrate a need for devising new treatment strategies to improve healing of flexor tendon insertion site injuries. © 2002 Orthopaedic Research Society. Published by Elsevier Science Ltd. All rights reserved.
Evaluation of an external device measuring knee joint rotation: an in vivo study with simultaneous Roentgen stereometric analysis
Authors: Almquist Per O. , Arnbjörnsson Arnbjörn , Zätterström Rose , Ryd Leif , Ekdahl Charlotte , Fridén Thomas
Published: October 2002

An external device (“rottometer”) specially designed to measure knee joint rotation was developed and evaluated with respect to its validity. Simultaneous measurements were made with the rottometer and Roentgen stereometric analysis (RSA) in five patients with implanted tantalum markers in the tibia and femur. Measurements of internal and external rotation were made at 90° and 60° of knee flexion using 3, 6 and 9 N m torques. The coefficients of determination (r2) between the results obtained with the rottometer and RSA were around 0.9 for the total rotation. The rottometer consistently overestimated the rotation by about 100% and this systematic error was most constant at 90° flexion for the different torques. The magnitude of this error from soft tissue deformation as well as the rotatory movements in the hip, foot and ankle joints must be considered when using external devices to measure knee rotation in clinical studies. The most accurate registrations were found in 90° flexion with 9 N m force (r2 = 0.94). © 2002 Orthopaedic Research Society. Published by Elsevier Science Ltd. All rights reserved.
In vivo fatigue loading of the rat ulna induces both bone formation and resorption and leads to time‐related changes in bone mechanical properties and density
Authors: Hsieh Yeou‐Fang , Silva Matthew J.
Published: October 2002

Fatigue loading triggers bone resorption and is associated with stress fractures. Neither the osteogenic response nor the changes in bone mechanical properties following in vivo fatigue loading have been quantified. To further characterize the skeletal response to fatigue loading, we assessed bone formation, mechanical properties, density and resorption in the ulnae of 72 adult rats subjected to a single bout of in vivo loading followed by 0, 6, 12 or 18 days of recovery. Axial, compressive loading (peak force 13.3 N, 2 Hz) was applied to the right forelimb until the ulna was fatigued to a pre‐determined level. The left forelimb served as a contralateral control. The primary osteogenic response to fatigue loading was woven bone formation that occurred on the periosteal surface of the ulnar diaphysis and was significantly greater in loaded limbs versus controls at 6, 12 and 18 days (p < 0.05). Ultimate force of the ulna in three‐point bending decreased by 50% and stiffness decreased by 70% on day 0 (p < 0.01 vs. control), indicative of acute fatigue damage. By day 12, ultimate force and stiffness had returned to control levels (p > 0.05) and by day 18 had increased 20% beyond controls (p < 0.01). Bone cross‐sectional area, moment of inertia, and mineral content increased with recovery time (p < 0.01), consistent with the increases in woven bone formation and mechanical properties. Intracortical resorption space density and osteoclast density also increased with recovery time (p < 0.05), indicating activation of intracortical remodeling. In summary, our findings demonstrate the remarkable ability of the adult skeleton to rapidly form periosteal woven bone and thereby offset the negative structural effects of acute fatigue damage and subsequent intracortical resorption. © 2002 Orthopaedic Research Society. Published by Elsevier Science Ltd. All rights reserved.
Bone consolidation is enhanced by rhBMP‐2 in a rabbit model of distraction osteogenesis
Authors: Li Gang , Bouxsein Mary L. , Luppen Cynthia , Li X. Jian , Wood Martin , Seeherman Howard J. , Wozney John M. , Simpson Hamish
Published: October 2002

Recombinant human bone morphogenetic protein‐2 (rhBMP‐2) is a differentiation factor which has been shown to induce bone formation and heal bony defects in a variety of animal models. A possible application of rhBMP‐2 is to accelerate bone regeneration during distraction osteogenesis, which clinically is a long procedure, often involving significant complications. In this study we tested the ability of rhBMP‐2 to accelerate the consolidation phase of distraction osteogenesis in a rabbit model of leg lengthening. Tibiae were lengthened 2 cm over a period of ten days. rhBMP‐2 was administered at the end of the lengthening phase. Two modes of rhBMP‐2 application were tested: surgical implantation of rhBMP‐2/ACS (absorbable collagen sponge) into the regenerate (50 μl of 1.5 mg/ml rhBMP‐2, total dose = 75 μg rhBMP‐2), and percutaneous injection of rhBMP‐2/buffer (0.1 ml of 0.75 mg/ml rhBMP‐2, total dose = 75 μg rhBMP‐2) into three sites within the regenerate. Also, there were three groups of control animals: (1) no surgical intervention, (2) surgical implantation of buffer/ACS and (3) percutaneous injection of buffer. Rabbits were sacrificed at 5, 14 and 28 days after the interventions. Radiographic evaluation indicated a significant increase in bony union of the distraction regenerate in the rhBMP‐2 treated groups compared with the untreated groups at 5 and 14 days. At 28 days, formation of a cortex and reestablishment of the medullary canal was evident only in the rhBMP‐2 treated groups. The bone mineral content (BMC) of the regenerate was significantly higher in the rhBMP‐2 treated groups at 5 and 14 days. However, at 28 days, BMC of the regenerate was similar in all groups. The average volumetric density of the regenerate was significantly higher in the rhBMP‐2 injection group at day 14. In summary, both injection of rhBMP‐2/buffer and implantation of rhBMP‐2/ACS enhanced the consolidation stage of distraction osteogenesis in this rabbit model. © 2002 Orthopaedic Research Society. Published by Elsevier Science Ltd. All rights reserved.
Factors influencing changes in articular cartilage following hemiarthroplasty in sheep
Authors: van der Meulen Marjolein C. H. , Beaupré Gary S. , Smith R. Lane , Giddings Virginia L. , Allen William A. , Athanasiou Kyriacos A. , Zhu Chong Fang , Song Yong , Mandell Jay A. , Poser Robert D. , Goodman Stuart B.
Published: October 2002

This study examined the relationship between acetabular cartilage properties after hemiarthroplasty surgery and surgical variables including femoral head size and position. Nineteen sheep received unilateral hip arthroplasties and were euthanized one year post‐operatively to harvest the femora and acetabula. Cartilage histology, biochemistry and material properties were determined from samples located in the superior load‐bearing region. Femoral head size mismatch, leg length difference, anterior‐posterior and medial‐lateral offset and anteversion were measured. In the acetabulum, substantial cartilage degradation occurred with widespread fibrillation and significant changes in the biochemical and material properties compared to the intact contralateral joint. Regression analyses on the surgical variables explained 75–80% of the changes in tissue biochemistry but did not explain the material changes. Head size mismatch and leg length difference were the most significant contributors of the five variables examined and therefore may be critical to successful outcome in hemiarthroplasty. © 2002 Orthopaedic Research Society. Published by Elsevier Science Ltd. All rights reserved.
Acute heart failure: a novel approach to its pathogenesis and treatment
Authors: Cotter Gad , Moshkovitz Yaron , Milovanov Olga , Salah Ahmed , Blatt Alex , Krakover Ricardo , Vered Zvi , Kaluski Edo
Published: October 2002

Acute heart failure (HF) is one of the most common syndromes in emergency medicine, however, its exact pathogenesis has remained largely unknown. Based on clinical and hemodynamic data we have sub‐divided acute HF into four syndromes: cardiogenic shock, pulmonary edema, hypertensive crisis and exacerbated HF. Cardiogenic shock is caused by a severe reduction in cardiac power which is not met by an adequate increase in peripheral vascular resistance leading to significant decrease in blood pressure and end organ perfusion. Hence the treatment of cardiogenic shock should be directed at improving cardiac performance (by optimizing filling pressure, intra‐aortic balloon pump and immediate revascularization) and administration of peripheral vasoconstrictors. The other acute HF syndromes (pulmonary edema, HTN crisis and exacerbated HF) are caused by a combination of progressive excessive vasoconstriction superimposed on reduced left ventricular functional reserve. The impaired cardiac power and extreme vasoconstriction induce a vicious cycle of afterload mismatch resulting in a dramatic reduction of CO and elevated left ventricular end diastolic pressure, which is transferred backwards to the pulmonary capillaries yielding pulmonary edema. Therefore, the immediate treatment of these acute HF syndromes should be based on the administration of strong, fast‐acting intravenous vasodilators such as nitrates or nitroprusside. After initial stabilization, therapy should be directed at reducing recurrent episodes of acute HF, by prevention of repeated episodes of excessive vasoconstriction along with efforts to optimize cardiac function.
Doppler‐echocardiographic indices of diastolic function in heart failure admissions with preserved left ventricular systolic function
Authors: Cahill John M. , Horan Mairead , Quigley Peter , Maurer Brian J. , McDonald Ken
Published: October 2002

Many patients admitted to hospital with heart failure have preserved left ventricular (LV) systolic function. The incidence of isolated diastolic dysfunction as a cause of such admission remains unclear. We aimed to examine diastolic function in unselected admissions from the community with heart failure using the European Study Group on Diastolic Heart Failure (ESGDHF) Doppler‐echocardiographic indices of diastolic dysfunction. Primary heart failure was confirmed in 210 of 309 sequential admissions with suspected heart failure. Doppler echocardiography was used to assess left ventricular ejection fraction, wall thickness and parameters of diastolic function including E:A ratio, E‐wave deceleration time and isovolumic relaxation time. Of 210 patients studied (118 female), ejection fraction was <45% in 111, leaving a population of 99 with preserved systolic function. We excluded those with significant valvular disease, leaving 56 patients (mean age‐77 years) with an ejection fraction >45% and no other relevant abnormality. Twenty were in atrial fibrillation. E‐wave deceleration time was >280 ms in 42%. E:A was reversed in 30 of 36 patients in sinus rhythm, but only seven met the ESGDHF criterion of E:A<0.5. Isovolumic relaxation time was >105 ms in 38%. Wall thickness was increased in 75% of cases. The ESGDHF Doppler‐echocardiographic criteria for diastolic heart failure were fulfilled in 43%. In clinically confirmed heart failure, 27% of patients had preserved systolic function and no significant valvular disease. Only 43% of this group had confirmed diastolic heart failure by these ESGDHF criteria. The pathophysiological basis of the syndrome in the remaining 57% remains unclear.
Is beta‐blockade useful in heart failure patients with atrial fibrillation? An analysis of data from two previously completed prospective trials
Authors: Fung Jeffrey W.H. , Chan Skiva K.W. , Yeung Leata Y.C. , Sanderson John E.
Published: October 2002

Background

Beta‐adrenergic blockade is of proven value in chronic heart failure. It is uncertain, however, if beta‐blockade provides a similar degree of clinical benefit for heart failure patients with atrial fibrillation (AF) as those in sinus rhythm (SR).

Aims

To compare the effectiveness of beta blockade in patients with heart failure and AF.

Methods

Patients with chronic heart failure were randomized to treatment (double blind) with metoprolol 50 mg twice daily or carvedilol 25 mg twice daily in addition to standard therapy. Response was assessed after 12 weeks by a quality of life questionnaire, New York Heart Association class, exercise capacity (6‐min walk test), radionucleotide ventriculography for LVEF, 2‐D echocardiography measurement of left ventricular (LV) dimensions and diastolic filling and 24‐h electrocardiograph monitoring to assess heart rate changes.

Results

Both beta‐blockers produced significant improvements in LVEF in both the SR group: (+6±10% at 12‐week, P<0.001) and the AF group: (+11±9% at 12‐week, P<0.05). However, significant improvement in symptoms (P<0.001) and exercise capacity (P<0.001) were observed only in the SR group but not in the AF group despite a significant improvement in LVEF.

Conclusion

Beta‐blockers were effective in improving LV ejection fraction in chronic heart failure patients in either SR or AF but had less effect on symptoms and exercise capacity in those with AF.
Regional Allocation of Structural Funds in the European Union
Authors: Gil Carlos , Pascual Pedro , Rapún Manuel
Published: October 2002

Economic disparities among the regions of the European Union are more pronounced than among countries. Structural Funds have played a crucial compensatory role, promoting the economic development and real convergence of lagging regions. The amount of resources destined to regional policy and the conflicts arising from its funding and distribution create the need for an adequate theoretical foundation or model to help politicians solve the distribution problem. In this paper we propose an empirical procedure to carry out and evaluate different distributions of funds for the periods 1989 – 93 and 1994 – 99. We begin with the estimation of an augmented production function to permit the calculation of the expected GDP per capita. We then propose a nonlinear programming method to simulate alternative distributions of Structural Funds among Objective 1 regions, based upon two different approaches: equal development, and equal opportunities. For these two approaches we calculate different possibilities, ranging from highly efficient to highly equitable, with the result that we are able to show the ‘frontier’ of optimal distributions. Finally, we evaluate these results and compare them with the real distribution.
Task Forces and the Organisation of Economic Development: The Case of the North East Region of England
Authors: Pike Andy
Published: October 2002

The task force has emerged as a mechanism for coordinating economic development activity in the context of the current New Labour government's emphasis upon including ‘stakeholders’ in ‘joined-up’ approaches to ‘crosscutting’ issues. In this paper I examine the use of task forces to organise economic development at employer, sectoral, and territorial levels at the local and regional scales in the North East region of England. It is argued that New Labour's experimental use of task forces reflects a particular mediation of more general tendencies in the historical evolution of state modernisation, which varies in particular and contingent ways at the local and regional levels. The research reveals the continued importance of the existing public-sector and public—private-sector institutions, the less significant and contingent role of the private sector, and the contribution of the task force to the ‘quasi-governance’ of the United Kingdom, with its problems of coordination, transparency, and accountability. A renewed politics of economic development governance is required to establish the accountability and legitimacy of such bodies in the context of the emergent multilayered governance system of the UK political economy.
Myogenic specification of side population cells in skeletal muscle
Authors: Asakura Atsushi , Seale Patrick , Girgis-Gabardo Adele , Rudnicki Michael A.
Published: October 2002

Skeletal muscle contains myogenic progenitors called satellite cells and muscle-derived stem cells that have been suggested to be pluripotent. We further investigated the differentiation potential of muscle-derived stem cells and satellite cells to elucidate relationships between these two populations of cells. FACS® analysis of muscle side population (SP) cells, a fraction of muscle-derived stem cells, revealed expression of hematopoietic stem cell marker Sca-1 but did not reveal expression of any satellite cell markers. Muscle SP cells were greatly enriched for cells competent to form hematopoietic colonies. Moreover, muscle SP cells with hematopoietic potential were CD45 positive. However, muscle SP cells did not differentiate into myocytes in vitro. By contrast, satellite cells gave rise to myocytes but did not express Sca-1 or CD45 and never formed hematopoietic colonies. Importantly, muscle SP cells exhibited the potential to give rise to both myocytes and satellite cells after intramuscular transplantation. In addition, muscle SP cells underwent myogenic specification after co-culture with myoblasts. Co-culture with myoblasts or forced expression of MyoD also induced muscle differentiation of muscle SP cells prepared from mice lacking Pax7 gene, an essential gene for satellite cell development. Therefore, these data document that satellite cells and muscle-derived stem cells represent distinct populations and demonstrate that muscle-derived stem cells have the potential to give rise to myogenic cells via a myocyte-mediated inductive interaction.
Nogo-A expressed in Schwann cells impairs axonal regeneration after peripheral nerve injury
Authors: Pot Caroline , Simonen Marjo , Weinmann Oliver , Schnell Lisa , Christ Franziska , Stoeckle Sascha , Berger Philipp , Rülicke Thomas , Suter Ueli , Schwab Martin E.
Published: October 2002

Înjured axons in mammalian peripheral nerves often regenerate successfully over long distances, in contrast to axons in the brain and spinal cord (CNS). Neurite growth-inhibitory proteins, including the recently cloned membrane protein Nogo-A, are enriched in the CNS, in particular in myelin. Nogo-A is not detectable in peripheral nerve myelin. Using regulated transgenic expression of Nogo-A in peripheral nerve Schwann cells, we show that axonal regeneration and functional recovery are impaired after a sciatic nerve crush. Nogo-A thus overrides the growth-permissive and -promoting effects of the lesioned peripheral nerve, demonstrating its in vivo potency as an inhibitor of axonal regeneration.
Eddy currents in thin plates modelled as surface regions
Authors: Fireteanu Virgiliu , Paya Bernard , Nuns Jacques , Tudorache Tiberiu
Published: October 2002

This paper analyses the conditions for which the results of eddy currents computation in thin regions modelled by surface regions are concordant with those obtained using volume finite elements. The concepts of geometrically thin or thick region, electromagnetically thin or thick region, 2D or 3D problem, transverse or longitudinal flux problem are used to characterise the limits of the surface model. The computation of eddy currents in sheets heated in transverse flux inductors and of the eddy current losses in metallic casing of an induction furnace highlights the surface finite element applicability.
Field and current flow analysis of the buried feeding line of the innovative electric transport concept STREAM
Authors: Alotto P. , Delfino F. , Molinari G. , Rossi M. , Siciliano V. , Ventura P.O.
Published: October 2002

STREAM is the acronym of a new concept of mass transit system designed and developed by Ansaldo Trasporti S.p.A. to provide an efficient solution to rubber‐tyred transportation problems in urban areas. One of STREAM's most distinctive feature is the power supply system, which uses a magnetic lift contact line embedded in the road surface to deliver traction power and to provide operating and control information. In this paper the field and the current flow analyses of this buried feeding track are presented and discussed. Analyses are aimed at determining the highest values of accessible voltages on the ground under different environmental and operating conditions. Results provided by a numerical simulation of the 3D model representing the feeding track allow us to identify the most critical conditions and to verify the safety and reliability of the system.
3D‐FDTD characterization of an original low‐loss silicon line
Authors: Richardson Alexandre , Cirio Laurent , Martoglio Laurent , Picon Odile
Published: October 2002

A numerical and experimental analysis of an original inverted microstrip transmission line on standard Silicon substrate for telecommunication applications is proposed. Simulations have been made using a time domain method such as Finite‐Difference‐Time‐Domain method (FDTD) to obtain results on a large frequency band. However, the main difficulty of the FDTD is due to the absorbing boundary conditions (ABC) which must be perfectly matched to the inhomogeneous media with losses. Indeed, the fine dimensions prescribed by the studied circuit lead to a long computational time. To reduce the FDTD grid but also to simulate inhomogeneous medium with losses, an efficient and broadband ABC has to be implemented because classical ones are not suitable to simulate a lossy substrate. For this reason, a specific uniaxial perfectly matched layers (UPML) is proposed. We compare numerical results obtained with FDTD, HP Momentum and experimental ones to show the validation of the method applied to lossy media.
Evaluation of TQM in Japanese industries and validation of a self‐assessment questionnaire
Authors: da Silva Jonas Gomes , Kikuo Nezu , Tadashi Ohfuji
Published: October 2002

Provides empirical support for TQM reviewing and improvement. Evaluates 190 companies’ performance that have or have not used TQM in Japan. Cross‐sectional survey methodology is employed. Thus, seven categories with 80 key elements regarding American MBNQA and ten equations are examined. The main conclusions are that, although TQM remains helpful for Japanese business performance, globalization has created a highly competitive environment where companies using only TQM (or another single management system) will not be able to survive in the long term; and that the examined self‐assessment questionnaire, although far from 100 per cent perfect, is a reliable and valid instrument for calculating business performance.
Reactivation of Ca2+‐dependent cytoplasmic contraction in permeabilized cell models of the heliozoon Echinosphaerium akamae
Authors: Arikawa Mikihiko , Suzaki Toshinobu
Published: October 2002

Permeabilized cell models of the large heliozoon Echinosphaerium akamae were prepared by treatment with 100 mM EGTA or 1% Triton X‐100. When > 10‐6 M Ca2+ was added to the EGTA‐permeabilized cells, axopodial cytoplasm became contracted and several swellings were formed along the axopodial length. Axonemal microtubules remained intact, while higher concentration of Ca2+ (> 10‐4 M) induced microtubule disassembly and complete breakdown of the axopodia. In Triton‐permeabilized cells, cytoplasmic contraction and relaxation of the cell body were induced repeatedly by successive addition and removal of Ca2+. The contraction did not require ATP, and was not inhibited by cytochalasin B. Electron microscopy showed, in EGTA‐permeabilized axopodia, contractile tubules became granulated by the addition of Ca2+. From these observations, it is strongly suggested that Ca2+‐dependent granulation of the contractile tubules is responsible for the axopodial contraction. Cell Motil. Cytoskeleton 53:267–272, 2002. © 2002 Wiley‐Liss, Inc.
Trajectorial organisation of cytokeratins within the subapical region of umbrella cells
Authors: Veranič Peter , Jezernik Kristijan
Published: October 2002

The subapical region of umbrella cells in the urinary bladder contains a dense cytokeratin (CK) network. Yet, this network should enable a very intensive traffic of specific fusiform vesicles involved in alterations of the surface area of the apical membrane. Therefore, the cytokeratins should be organised in a way to be both mechanically strong and also passable for fusiform vesicles. The supramolecular organisation of the CKs in the subapical region of umbrella cells in mice was studied by conventional fluorescence, confocal laser microscopy, and TEM. It has been found that the first 150 to 300 nm under the apical membrane is filled with fusiform vesicles and only below that the CK network begins. The CK 7 and CK 20 compose a subapical network, which is created as an array of parallel trajectories pointing to the apical plasma membrane. The network is framed by a strong wall of CK, which is parallely aligned in neighbouring cells. The double labelling of the urothelial‐specific membrane proteins, uroplakins, and CKs proved the presence of fusiform vesicles within these trajectories. The measurements proved that the trajectory diameter in the upper half of the network is smaller than in the lower half. The diameters of the trajectories in animals with distended bladders exceeded those in contracted bladders for 70%, which most likely facilitates the transport of fusiform vesicles to the apical membrane. Discovery of the subapical CK network elucidates the until now undescribed supramolecular organisation of CKs in the apical region of urothelial cells. Cell Motil. Cytoskeleton 53:317–325, 2002. © 2002 Wiley‐Liss, Inc.