bluuebunny/crossref_metadata_2025 huggingface dataset:
Outcome of Charnley total hip replacement across a single health region in England
Authors: Allami M. K. , Fender D. , Khaw F. M. , Sandher D. R. , Esler C. , Harper W. M. , Gregg P. J.
Published: September 2006

Using the Trent regional arthroplasty register, we analysed the survival at ten years of 1198 consecutive Charnley total hip replacements carried out across a single health region of the United Kingdom in 1990. At ten years, information regarding outcome was available for 1001 hips (83.6%). The crude revision rate was 6.2% (62 of 1001) and the cumulative survival rate with revision of the components as an end-point was 93.1%. At five years, a review of this series of patients identified gross radiological failure in 25 total hip replacements which had previously been unrecognised. At ten years the outcome was known for 18 of these 25 patients (72%), of whom 13 had not undergone revision.

This is the first study to assess the survival at ten years for the primary Charnley total hip replacement performed in a broad cross-section of hospitals in the United Kingdom, as opposed to specialist centres. Our results highlight the importance of the arthroplasty register in identifying the long-term outcome of hip prostheses.
Single-stage revision of peri-prosthetic infection following total elbow replacement
Authors: Gille J. , Ince A. , González O. , Katzer A. , Loehr J. F.
Published: September 2006

This study reviews the predisposing features, the clinical, and laboratory findings at the time of diagnosis and the results of single-stage revision of prosthetic replacement of the elbow for infection.

Deep infection occurred in six of 305 (1.9%) primary total elbow replacements. The mean follow-up after revision was 6.8 years (6 months to 16 years) and the mean age at the time of revision was 62.7 years (56 to 74). All six cases with infection had rheumatoid arthritis and had received steroid therapy. The infective organism was Staphylococcus aureus. Four of the six elbows had a developed radiolucency around one component or the other. Successful single-stage exchange arthroplasty was carried out with antibiotic-loaded cement in five of the six cases. In one, the revision prosthesis had to be removed following recurrence of the infection. The functional result was good in three elbows, fair in one, poor in one and fair in the resection arthroplasty.
The impact of tobacco use and body mass index on the length of stay in hospital and the risk of post-operative complications among patients undergoing total hip replacement
Authors: Azodi O. Sadr , Bellocco R. , Eriksson K. , Adami J.
Published: September 2006

We carried out a retrospective cohort study of 3309 patients undergoing primary total hip replacement to examine the impact of tobacco use and body mass index on the length of stay in hospital and the risk of short term post-operative complications.

Heavy tobacco use was associated with an increased risk of systemic post-operative complications (p = 0.004). Previous and current smokers had a 43% and 56% increased risk of systemic complications, respectively, when compared with non-smokers. In heavy smokers, the risk increased by 121%. A high body mass index was significantly associated with an increased mean length of stay in hospital of between 4.7% and 7%. The risk of systemic complications was increased by 58% in the obese. Smoking and body mass index were not significantly related to the development of local complications.

Greater efforts should be taken to reduce the impact of preventable life style factors, such as smoking and high body mass index, on the post-operative course of total hip replacement.
Secreted Frizzled-Related Protein 4 Is a Negative Regulator of Peak BMD in SAMP6 Mice
Authors: Nakanishi Rika , Shimizu Motoyuki , Mori Masayuki , Akiyama Haruhiko , Okudaira Shuzo , Otsuki Bungo , Hashimoto Maiko , Higuchi Keiichi , Hosokawa Masanori , Tsuboyama Tadao , Nakamura Takashi
Published: September 2006

We segregated a QTL for peak BMD on Chr 13 by generating congenic sublines of the senescence-accelerated mouse SAMP6. Sfrp 4 within this locus was responsible for lower BMD of SAMP6.

Introduction: Our genome-wide linkage study using SAMP6 and SAMP2 showed a significant quantitative trait locus (QTL) for peak BMD on chromosome (Chr) 13. To verify the gene that regulates peak BMD, we generated a congenic strain, P6.P2-Pbd2b, which carried a 15-cM SAMP2 interval on an osteoporotic SAMP6 background, and showed that this Pbd2 locus increased peak BMD in SAMP6.

Materials and Methods: To narrow down this interval, we generated a new congenic subline P6.P2–13. We studied the effect of this locus on morphological and histomorphological features in vivo and on osteoblasts in vitro. The levels of expression of all genes in the segregated interval were examined, and we clarified the effect of the candidate gene, secreted frizzled-related protein (Sfrp4), on osteoblasts in vitro.

Results: The new congenic strain, P6.P2–13, retained the 2.4-Mb SAMP2 interval on the SAMP6 background, and 11 genes existed in this interval. In morphometrical analysis, P6.P2–13 increased the bone area fraction (BA/TA) by 6.6% at the diaphysial cortex (p < 0.001) and increased the trabecular bone volume (BV/TV) by 54.2% at the distal metaphysis (p < 0.05) in the femora compared with those of SAMP6. The bone formation rate of P6.P2–13 was markedly increased at the periosteal surface of femoral cortex and that was caused by a higher proliferation rate of osteoblasts in P6.P2–13 compared with those in SAMP6. Quantitative RT-PCR analysis of calvaria tissue showed ∼40-fold higher levels of expression of Sfrp4 in SAMP6 than in P6.P2–13. Taken together with the result that recombinant Sfrp4 suppressed the proliferation of osteoblasts, we hypothesized that Sfrp4 inhibited the proliferation of osteoblasts through its antagonistic effect on Wnt signaling. TCF/β-catenin–dependent reporter activity in osteoblasts derived from SAMP6 showed lower responsiveness for the Wnt ligand, Wnt3A, than that in osteoblasts from P6.P2–13.

Conclusions: In SAMP6 mice, Sfrp4 negatively regulates bone formation and decreases BMD through the inhibition of Wnt signaling.
Reduced Peripheral Nerve Function Is Related to Lower Hip BMD and Calcaneal QUS in Older White and Black Adults: The Health, Aging, and Body Composition Study
Authors: Strotmeyer Elsa S , Cauley Jane A , Schwartz Ann V , de Rekeneire Nathalie , Resnick Helaine E , Zmuda Joseph M , Shorr Ronald I , Tylavsky Frances A , Vinik Aaron I , Harris Tamara B , Newman Anne B ,   for the Health ABC Study
Published: September 2006

Bone tissue is innervated, and peripheral nerve function may impact BMD. Older black and white men and women (N = 2200) in the Health, Aging, and Body Composition Study with worse sensory and motor peripheral nerve function had lower hip BMD and calcaneal BUA independent of lean mass, strength, physical ability, and diabetes. Poor peripheral nerve function may directly affect bone.

Introduction: Bone tissue is innervated, yet little is known about the impact of nerve function on BMD. Poor peripheral nerve function may contribute to lower BMD and higher fracture risk, particularly in those with diabetic neuropathy.

Materials and Methods: The Health, Aging, and Body Composition (Health ABC) Study included annual exams in white and black men and women 70–79 years of age recruited from Pittsburgh and Memphis. Nerve function in legs/feet was assessed by 1.4- and 10-g monofilament detection, vibration threshold, and peroneal motor nerve conduction velocity (NCV) and amplitude (CMAP). Total hip BMD, heel broadband ultrasound attenuation (BUA), and total fat and lean mass were measured 1 year later (QDR 4500A, Sahara QUS; Hologic).

Results: Participants (N = 2200) were 48% men and 37% black. Poor nerve function (lower monofilament detection, higher vibration threshold, lower CMAP, lower NCV) was associated with 1.4–5.7% lower BUA and significant for all but NCV, adjusted for demographics, diabetes, body composition, and physical ability. Results were similar for adjusted hip BMD, with 1.0–2.9% lower BMD, significant for monofilament and CMAP testing. When considering the components of BMD, total hip area was 1.8–4.9% higher in those with the worst nerve function, although BMC showed little difference. Lower monofilament detection and CMAP were independently associated with lower heel BUA (p < 0.01), and monofilament detection was associated with lower hip BMD (p < 0.05) in regression additionally adjusted for lifestyle factors, bone-active medications, and diabetes-related complications.

Conclusions: Poor peripheral nerve function may directly related to lower BMD, likely through an increase in bone area in older adults, independent of lean mass, strength, physical ability, and diabetes. Whether those with impaired nerve function are at higher risk for fracture independent of falls needs to be studied.
T Lymphocyte–Deficient Mice Lose Trabecular Bone Mass With Ovariectomy
Authors: Lee Sun-Kyeong , Kadono Yuho , Okada Fumihiko , Jacquin Claire , Koczon-Jaremko Boguslawa , Gronowicz Gloria , Adams Douglas J , Aguila Hector L , Choi Yongwon , Lorenzo Joseph A
Published: September 2006

We examined OVX-induced bone loss in three TLD mouse models. In TLD mice, OVX caused trabecular bone loss equivalent to that of WT. In contrast, cortical bone loss with OVX was variable. We conclude that T lymphocytes do not influence OVX-induced trabecular bone loss.

Introduction: We examined ovariectomy (OVX)-induced bone loss in three T lymphocyte–deficient (TLD) mouse models: nude mice, recombination activating gene 2–deficient (RAG2 KO) mice, and T cell receptor α chain–deficient (TCRα KO) mice.

Materials and Methods: Bone mass was examined by DXA, μCT, and histomorphometry. We also examined the effect of OVX on T lymphocytes in the bone marrow and spleens of wildtype (WT) mice and on in vitro osteoclastogenesis and colony forming unit-granulocyte macrophage (CFU-GM) activity in the bone marrow of WT and nude mice.

Results: In WT mice, OVX did not alter T lymphocyte number in the bone marrow but did increase T lymphocytes in the spleen. Comparison of bone mass in nude, RAG2 KO, and TCRα KO mice with WT as measured by DXA showed decreased femoral bone mass in nude mice and increased vertebral bone mass in RAG2 KO mice. In TCRα KO mice, femoral, tibial, and vertebral bone mass were decreased. In vertebrae and long bones, bone loss with OVX was consistently present in WT mice but variably present in TLD mice as measured by DXA. In contrast, μCT and histomorphometry showed similar trabecular bone loss after OVX in all mice. However, femoral cortical bone loss occurred only in WT and RAG2 KO mice. OVX produced similar trabecular bone loss in WT and TCRα KO mice and also induced cortical bone loss in both. Histomorphometry showed that TRACP+ area in bones was increased by OVX in femurs from both WT and nude mice as was in vitro osteoclast-like cell formation and CFU-GM activity.

Conclusions: These results show that OVX caused similar trabecular bone loss in both WT and TLD mice. The ability of DXA and measurement of cortical bone loss to show OVX-induced effects on bone mass was variable. It seems that T lymphocytes are not critical for OVX-induced trabecular bone loss in these mouse models.
Nationwide Decline in Incidence of Hip Fracture
Authors: Kannus Pekka , Niemi Seppo , Parkkari Jari , Palvanen Mika , Vuori Ilkka , Järvinen Markku
Published: September 2006

This epidemiologic study determined the trend in the number and incidence (per 100,000 persons) of hip fracture among older adults in Finland, an EU country with a well-defined white population of 5.2 million, between 1970 and 2004. The results show that the alarming rise in the fracture incidence from early 1970s until late 1990s has been now followed by declining fracture rates. Reasons for this are largely unknown, but a cohort effect toward a healthier aging population and increased average body weight and improved functional ability among elderly Finns could partly explain the phenomenon.

Introduction: Although osteoporotic fractures of older adults are said to be a major public health concern in modern societies with aging populations, fresh nationwide information on their secular trends is limited.

Materials and Methods: This epidemiologic study determined the current trend in the number and incidence (per 100,000 persons) of hip fracture among older adults in Finland, an EU country with a well-defined white population of 5.2 million, by taking into account all persons ≥50 years of age who were admitted to our hospitals for primary treatment of such fracture in 1970–2004.

Results: The number of hip fractures among ≥50-year-old Finns rose very constantly between 1970 (1857 fractures) and 1997 (7122 fractures), but since then, the rise has leveled off (7083 fractures in 2004). After this and because of a continuous rise in population at risk, the crude incidence of hip fracture (showing a clear rise in 1970–1997) decreased between 1997 and 2004, from 438 (per 100,000 persons) in 1997 to 374 in 2004. Concerning the age-adjusted fracture incidence, findings were similar. Until 1997, the age-adjusted incidence of hip fracture clearly increased in both women and men, but thereafter, this incidence declined in both sexes: in women, from 494 in 1997 to 412 in 2004, and in men, from 238 in 1997 to 223 in 2004.

Conclusions: The rise in the incidence of hip fracture in Finland from the early 1970s until the late 1990s has been followed by declining fracture rates. Exact reasons for this are unknown, but a cohort effect toward a healthier aging population and increased average body weight and improved functional ability among elderly Finns cannot be ruled out.
Clinical Vignette: Monostotic Fibrous Dysplasia of the Proximal Femur and Liposclerosing Myxofibrous Tumor: Which One Is Which?
Authors: Corsi Alessandro , De Maio Fernando , Ippolito Ernesto , Cherman Natasha , Robey Pamela Gehron , Riminucci Mara , Bianco Paolo
Published: September 2006

Clinical, histological, and genetic studies of two cases of isolated fibro-osseous lesions of the femur in adults show the overlap between monostotic fibrous dysplasia (MFD) of the proximal femur and the so-called liposclerosing myxofibrous tumor. The two cases highlight how the incomplete understanding of the natural history of MFD may result in diagnostic pitfalls or incorrect classification of individual lesions.
Advanced Molecular Profiling in Vivo Detects Novel Function of Dickkopf-3 in the Regulation of Bone Formation
Authors: Aslan Hadi , Ravid-Amir Osnat , Clancy Brian M , Rezvankhah Saeid , Pittman Debra , Pelled Gadi , Turgeman Gadi , Zilberman Yoram , Gazit Zulma , Hoffmann Andrea , Gross Gerhard , Domany Eytan , Gazit Dan
Published: September 2006

A bioinformatics-based analysis of endochondral bone formation model detected several genes upregulated in this process. Among these genes the dickkopf homolog 3 (Dkk3) was upregulated and further studies showed that its expression affects in vitro and in vivo osteogenesis. This study indicates a possible role of Dkk3 in regulating bone formation.

Introduction: Endochondral bone formation is a complex biological process involving numerous chondrogenic, osteogenic, and angiogenic proteins, only some of which have been well studied. Additional key genes may have important roles as well. We hypothesized that to identify key genes and signaling pathways crucial for bone formation, a comprehensive gene discovery strategy should be applied to an established in vivo model of osteogenesis.

Materials and Methods: We used in vivo implanted C3H10T1/2 cells that had been genetically engineered to express human bone morphogenetic protein-2 (BMP2) in a tetracycline-regulated system that controls osteogenic differentiation. Oligonucleotide microarray data from the implants (n =4 repeats) was analyzed using coupled two-way clustering (CTWC) and statistical methods. For studying the effects of dickkopf homolog 3 (Dkk3) in chondrogenesis and osteogenesis, C3H10T1/2 mesenchymal progenitors were used.

Results: The CTWC revealed temporal expression of Dkk3 with other chondrogenesis-, osteogenesis-, and Wnt-related genes. Quantitative RT-PCR confirmed the expression of Dkk3 in the implants. C3H10T1/2 cells that expressed Dkk3 in the presence of BMP2 displayed lower levels of alkaline phosphatase and collagen I mRNA expression than control C3H10T1/2 cells that did not express Dkk3. Interestingly, the levels of collagen II mRNA expression, Alcian blue staining, and glucose aminoglycans (GAGs) production were not influenced by Dkk3 expression. In vivo μCT and bioluminescence imaging revealed that co-expression of Dkk3 and BMP2 by implanted C3H10T1/2 cells induced the formation of significantly lower quantities of bone than cells expressing only BMP2.

Conclusions: A bioinformatics analysis enabled the identification of Dkk3 as a pivotal gene with a novel function in endochondral bone formation. Our results showed that Dkk3 might have inhibitory effects on osteogenesis, but no effect on chondrogenesis, indicating that Dkk3 plays a regulatory role in endochondral bone formation. Further mechanistic studies are required to reveal the mechanism of action of Dkk3 in endochondral bone formation.
Calcitonin Deficiency in Mice Progressively Results in High Bone Turnover
Authors: Huebner Antje K , Schinke Thorsten , Priemel Matthias , Schilling Sarah , Schilling Arndt F , Emeson Ronald B , Rueger Johannes M , Amling Michael
Published: September 2006

Although the pharmacological action of calcitonin (CT) as an inhibitor of bone resorption is well established, there is still some controversy regarding its physiological function. Unexpectedly, Calca-deficient mice lacking CT and α-calcitonin gene-related peptide (αCGRP) were described to have a high bone mass phenotype caused by increased bone formation with normal bone resorption. Here we show that these mice develop a phenotype of high bone turnover with age, suggesting that CT is a physiological inhibitor of bone remodeling.

Introduction: The absence of significant changes in bone mineral density caused by decline or overproduction of CT in humans has raised the question, whether the pharmacological action of CT as an inhibitor of bone resorption is also of physiological relevance. To study the physiological role of mammalian CT, we have analyzed the age-dependent bone phenotype of two mouse models, one lacking CT and αCGRP (Calca−/−), the other one lacking only αCGRP (αCGRP−/−).

Materials and Methods: Bones from wildtype, Calca−/−-mice and αCGRP−/−-mice were analyzed at the ages of 6, 12 and 18 months using undecalcified histology. Differences of bone remodeling were quantified by static and dynamic histomorphometry as well as by measuring the urinary collagen degradation products. To rule out secondary mechanisms underlying the observed phenotype, we determined serum concentrations of relevant hormones using commercially available antibody-based detection kits.

Results: Whereas αCGRP−/−-mice display an osteopenia at all ages analyzed, the Calca−/−-mice develop a phenotype of high bone turnover with age. Histomorphometric analysis performed at the age of 12 months revealed significant increases of bone formation and bone resorption specifically in the Calca−/−-mice. This severe phenotype that can result in hyperostotic lesions, can not be explained by obvious endocrine abnormalities other than the absence of CT.

Conclusions: In addition to the previously described increase of bone formation in the Calca-deficient mice, we have observed that there is also an increase of bone resorption with age. This suggests that CT has a dual action as an inhibitor of bone remodeling, which may explain why alterations of CT serum levels in humans do not result in major changes of bone mineral density.
Transmigration: A New Property of Mature Multinucleated Osteoclasts
Authors: Saltel Frédéric , Chabadel Anne , Zhao Yingshe , Lafage-Proust Marie-Hélène , Clézardin Philippe , Jurdic Pierre , Bonnelye Edith
Published: September 2006

Even though it is assumed that multinucleated osteoclasts are migrating cells on the bone surface to be resorbed, we show that they can also selectively transmigrate through layers of cells usually found in the bone microenvironment. This activity is associated with c-src and MMPs and can be stimulated by bone metastatic breast cancer cells, a process blocked by bisphosphonate treatment.

Introduction: Osteoclasts have an hematopoietic origin and are bone-resorbing cells. Monocytic precursors migrate to the bone surface where they fuse to form multinucleated osteoclasts able to migrate over the bone surface. We studied whether multinucleated osteoclasts were also able to transmigrate through tissues.

Materials and Methods: Murine spleen-derived and green fluorescent protein (GFP)-Raw derived osteoclasts were seeded on osteoblasts and several other cell types. The cells were fixed for 20 minutes, 4 or 12 h after osteoclast seeding, and stained with phalloidin to visualize actin using confocal microscopy. Drugs such as PP2 and GM6001, inhibitors of c-src and matrix metalloproteinases (MMPs), respectively, and risedronate were used to determine osteoclast transmigration regulating factors.

Results: We observed by confocal microscopy that multinucleated osteoclasts specifically transmigrate through confluent layers of various cell types present in the bone microenvironment in vitro. This is an efficient process associated with c-src and MMPs but is independent of podosomes. Moreover, conditioned medium from bone metastatic breast cancer cells stimulates osteoclast transmigration in vitro, a process inhibited by bisphosphonate treatment.

Conclusions: Our data describe a new property of mature multinucleated osteoclasts to transmigrate through various cell types. The ability to control this highly regulated osteoclast transmigration process may offer new therapeutic strategies for bone diseases associated with an imbalance in bone remodeling caused by excessive osteoclast resorption.
Evidence for Increased Clinical Severity of Familial and Sporadic Paget's Disease of Bone in Campania, Southern Italy
Authors: Rendina Domenico , Gennari Luigi , De Filippo Gianpaolo , Merlotti Daniela , de Campora Enrico , Fazioli Flavio , Scarano Gioacchino , Nuti Ranuccio , Strazzullo Pasquale , Mossetti Giuseppe
Published: September 2006

The analysis of 236 Italian patients with Paget's bone disease showed higher clinical severity and greater frequency of neoplastic degeneration among patients who live or descend from individuals living in the Campania region (southern Italy). A prevalent involvement of the spine and the skull, the sites preferentially involved in giant cell tumors complicating Paget's disease, was also shown in familial cases from this geographical region.

Introduction: The Campania region in southern Italy has been recently indicated as a high prevalence area for Paget's disease of bone (PDB), and most pagetic families with multiple occurrence of neoplasms in affected members were from this geographical region.

Materials and Methods: We evaluated the PDB epidemiological characteristics in 125 patients from Campania in comparison with 111 patients from other Italian regions. Twenty-three patients from Campania and 26 patients from other Italian areas had at least one first-degree relative affected by PDB (familial cases). The remaining patients made up the sporadic cases.

Results: Among subjects from Campania, the patients in the familial group tended to come from larger families and showed at diagnosis higher serum total alkaline phosphatase, larger extension of disease, and earlier mean age with respect to patients with PDB of the sporadic group. The skull, spine, and humerus were the sites preferentially involved in the familial cases. In contrast, no such differences were observed between familial and sporadic PDB cases among patients from the other geographical areas, except for a lower age at diagnosis. An increased PDB clinical severity was finally observed in the PDB cohort from Campania in comparison with patients from other Italian regions. Neoplastic degeneration of pagetic bones (osteosarcoma and giant cell tumor) was exclusively observed in patients with polyostotic PDB from Campania.

Conclusions: We showed a higher clinical severity of PDB with occurrence of neoplastic degeneration in the high prevalence area of Campania, with its maximum expression in cases with familial disease. This peculiar pattern might be traced to genetic predisposition and/or to the abnormal impact of a still undefined environmental trigger.
Accentuated Ovariectomy-Induced Bone Loss and Altered Osteogenesis in Heterozygous N-Cadherin Null Mice
Authors: Lai Chung Fang , Cheng Su-Li , Mbalaviele Gabriel , Donsante Christine , Watkins Marcus , Radice Glenn L , Civitelli Roberto
Published: September 2006

Ovariectomy-induced bone loss is accentuated in mice with germline Cdh2 haploinsufficiency, the result of a decreased osteoblastogenesis in the face of normal osteoclast number. Reduced N-cadherin abundance in these mice decreases cell—cell adhesion and alters signaling pathways important for osteoblast commitment and differentiation, thus providing in vivo evidence that N-cadherin—mediated cell—cell interactions are involved in homeostatic responses to increased bone remodeling.

Introduction: We have shown that targeted expression of a dominant negative truncated form of N-cadherin (Cdh2) delays acquisition of peak bone mass in mice and retards osteoblast differentiation. We tested the role of this molecule in the skeletal homeostatic response to ovariectomy in mice with germline Cdh2 haploinsufficiency.

Materials and Methods: Heterozygous Cdh2 null (Cdh2+/−) and wildtype mice were ovariectomized and followed up to 13 weeks by in vivo radiodensitometric and ex vivo histologic assessment of bone mass and turnover. Cells isolated from wildtype and Cdh2+/− mice were used to determine the alterations in bone cell function produced by partial loss of N-cadherin.

Results: Bone mass was not significantly different between Cdh2+/− and wildtype littermates, but on ovariectomy, bone loss in Cdh2+/− mice was initially slower, but with time it became significantly greater than in wildtype mice. This accentuated bone loss was associated with lower osteoblast number and serum osteocalcin levels, with no differences in bone resorption. Although development of calcified nodules was faster in calvaria cells isolated from Cdh2+/− mice relative to Cdh2+/+ cells, bone marrow osteogenic precursors were lower in the former than in the latter genotypes. Cdh2 expression was downregulated with differentiation in wildtype calvaria cells, whereas cadherin-11 abundance remained unchanged. Furthermore, cell—cell adhesion (postconfluence) was decreased among heterozygous calvaria cells, as was cell proliferation (preconfluence), relative to wildtype cells. Finally, the abundance and cellular distribution of β-catenin was minimally decreased in Cdh2+/− cells, whereas mitogen-activated protein kinase (MAPK) signaling was more active in Cdh2 insufficient cells.

Conclusions: Cdh2 is involved in the homeostatic bone formation response to ovariectomy, presumably by regulating osteoprogenitors number and differentiation through stabilization of cell—cell adhesion and/or signaling modulation.
Passing Ability Tester for Self-Consolidating Concrete
Authors: Dhonde HB , Mo YL , Hsu TTC
Published: September 2006

Passing ability is one of the most important workability properties of self-consolidating concrete (SCC) and self-consolidating fiber reinforced concrete (SCFRC). The popular J-ring apparatus which measures the passing ability indirectly in terms of the difference in drop levels or the unrestricted and restricted slump flow of SCC/SCFRC, could not determine the passing ability in a consistent manner. A simple, accurate, and practical passing ability tester (PAT) is proposed as a substitute to the conventionally used methods (J-ring, L-box, and U-box). PAT measures the passing ability directly and consistently by weighing the concrete that has passed through the reinforcing bar screen and expressing it as the percentage of the total concrete sampled. This paper presents the test results of various SCC/SCFRC mixes to verify the performance of PAT, including the correlation between the test results of PAT and J-ring.
Basics of Polymeric Scaffolds for Tissue Engineering
Authors: Agrawal CM , Carter J , Ong JL
Published: September 2006

This review article argues the case that there is a need for careful scaffold science for successful tissue engineering. Polymeric scaffolds should possess certain essential properties. However, these properties are not independent of each other and thus the development of a scaffold requires an optimization process. The article reviews several scaffold fabrication processes to highlight the complexity of the field. Issues related to porosity, permeability, and the need for adequate diffusion characteristics are discussed. Several previous studies on the effects of mixing in bioreactors are reviewed. Lastly, surface modification techniques are presented. In particular, recent work related to glow discharge gas plasma modification of biodegradable polymers is discussed.
Stem/Progenitor Cell-Specific Enhanced Green Fluorescent Protein Expression Driven by the Endogenous Mcm2 Promoter
Authors: Maslov Alexander Y. , Bailey Kimberly J. , Mielnicki Lawrence M. , Freeland Amy L. , Sun Xiaolei , Burhans William C. , Pruitt Steven C.
Published: September 2006

Previous studies have demonstrated expression of the minichromosome maintenance protein Mcm2 in cells that remain competent to divide, including stem/progenitor cells of the subventricular zone (SVZ) within the brain. Here, a transgenic mouse line in which the Mcm2 gene drives expression of enhanced green fluorescent protein (EGFP) was constructed by insertion of an internal ribosomal entry site (IRES)-EGFP cassette into the last exon of the gene, 3′ to the stop codon. In these mice, expression of EGFP is observed in the SVZ and several other tissues with high proliferative activity, including the spleen, intestine, hair follicles, and bone marrow. These observations suggest that EGFP fluorescence in this mouse line provides an index of the proliferative capacity of different tissues. Immunohistological analysis demonstrates a direct concordance between expression of EGFP and Mcm2, consistent with a transcriptional level downregulation of Mcm2 expression in postmitotic cells. To test the utility of EGFP expression for recovery of live cells retaining the capacity to divide, EGFP-expressing and -nonexpressing cells from bone marrow and brain were isolated from an adult Mcm2IRES-EGFP mouse by fluorescence-activated cell sorting and assayed for clonal growth. The EGFP-positive fraction contained the entire clonogenic population of the bone marrow and greater than 90% of neurosphere-forming cells from the brain. Brain-derived clonogenic cells were shown to remain competent to differentiate towards all three neural lineages. These studies demonstrate that the Mcm2IRES-EGFP transgenic line constructed here can be used for recovery of proliferation competent cells from different tissue types.
Survivin Identifies Keratinocyte Stem Cells and Is Downregulated by Anti-β1 Integrin During Anoikis
Authors: Marconi Alessandra , Dallaglio Katiuscia , Lotti Roberta , Vaschieri Cristina , Truzzi Francesca , Fantini Fabrizio , Pincelli Carlo
Published: September 2006

Survivin belongs to the family of inhibitor of apoptosis proteins and is involved in regulation of cell death as well as cell division. Here, we show that wild-type (WT) survivin is expressed in a subpopulation of basal keratinocytes in normal human skin at the cytoplasmic level. WT survivin is highly expressed in keratinocyte stem cells (KSCs), whereas its mRNA level decreases in transit amplifying (TA) cells and disappears in postmitotic (PM) cells. Likewise, WT survivin protein is expressed in KSCs, almost undetectable in TA cells, and absent in PM cells. Real time polymerase chain reaction demonstrates that the putative antiapoptotic isoforms survivin-2B and survivin-ΔEx3 are expressed at the highest levels in KSCs, whereas they tend to decrease in TA cells and disappear in PM cells. On the contrary, the putative proapoptotic variants of survivin, survivin-3B, and survivin-2α tend to be high in PM and TA cells and are almost absent in KSCs. By confocal microscopy, survivin is predominantly expressed at the nuclear level in KSCs, which proliferate significantly better than TA cells, which, in turn, express mostly cytosolic WT survivin. Blocking β1 integrin signal downregulates WT survivin mRNA and protein expression and induces apoptosis (anoikis) in KSCs. On the other hand, inhibition of β1 integrin upregulates mRNA expression of survivin-2α. Taken together, these results indicate that survivin identifies human KSCs. Expression of nuclear survivin could reflect the different behavior between KSCs in vitro and in vivo, in terms of proliferation. Finally, survivin could be part of the “niche” protection by preventing anoikis in KSCs.
Differentiation Potential of Parthenogenetic Embryonic Stem Cells Is Improved by Nuclear Transfer
Authors: Hikichi Takafusa , Wakayama Sayaka , Mizutani Eiji , Takashima Yasuhiro , Kishigami Satoshi , Van Thuan Nguyen , Ohta Hiroshi , Thuy Bui Hong , Nishikawa Shin-Ichi , Wakayama Teruhiko
Published: September 2006

Parthenogenesis is the process by which an oocyte develops into an embryo without being fertilized by a spermatozoon. Although such embryos lack the potential to develop to full term, they can be used to establish parthenogenetic embryonic stem (pES) cells for autologous cell therapy in females without needing to destroy normally competent embryos. Unfortunately, the capacity for further differentiation of these pES cells in vivo is very poor. In this study, we succeeded in improving the potential of pES cells using a nuclear transfer (NT) technique. The original pES cell nuclei were transferred into enucleated oocytes, and the resulting NT embryos were used to establish new NT-pES cell lines. We established 84 such lines successfully (78% from blastocysts, 12% from oocytes). All examined cell lines were positive for several ES cell markers and had a normal extent of karyotypes, except for one original pES cell line and its NT-pES cell derivatives, in which all nuclei were triploid. The DNA methylation status of the differentially methylated domain H19 and differentially methylated region IG did not change after NT. However, the in vivo and in vitro differentiation potentials of NT-pES cells were significantly (two to five times) better than the original pES cells, judged by the production of chimeric mice and by in vitro differentiation into neuronal and mesodermal cell lines. Thus, NT could be used to improve the potential of pES cells and may enhance that of otherwise poor-quality ES cells. It also offers a new tool for studying epigenetics.
Bone marrow aplasia—a rare complication of imatinib therapy in CML patients
Authors: Srinivas Upendra , Pillai Lakshmi S. , Kumar Rajat , Pati H.P. , Saxena Renu
Published: September 2006

Imatinib mesylate therapy in CML patients is a generally well tolerated without any significant hematological adverse drug effects. However, complications like anemia and cytopenias have been described in literature. A very few case reports of bone marrow aplasia following imatinib therapy have been reported so far. We here report five patients of CML who developed bone marrow aplasia following imatinib therapy. Am. J. Hematol., 2006. © 2006 Wiley‐Liss, Inc.
Effect of preoperative exercise on measures of functional status in men and women undergoing total hip and knee arthroplasty
Authors: Rooks Daniel S. , Huang Jie , Bierbaum Benjamin E. , Bolus Sarah A. , Rubano James , Connolly Christine E. , Alpert Sandra , Iversen Maura D. , Katz Jeffrey N.
Published: September 2006

Objective

To evaluate the effect of a short preoperative exercise intervention on the functional status, pain, and muscle strength of patients before and after total joint arthroplasty.

Methods

A total of 108 men and women scheduled for total hip arthroplasty (THA) or total knee arthroplasty (TKA) were randomized to a 6‐week exercise or education (control) intervention immediately prior to surgery. We assessed outcomes through questionnaires and performance measures. Analyses examined differences between groups over the preoperative and immediate postoperative periods and at 8 and 26 weeks postsurgery.

Results

Among THA patients, the exercise intervention was associated with improvements in preoperative Western Ontario and McMaster Universities Osteoarthritis Index function score (improvement of 2.2 in exercisers versus decline of 3.9 in controls; P = 0.02) and Short Form 36 physical function score (decline of 0.4 in exercisers versus decline of 14.3 in controls; P = 0.003). No significant differences were seen in TKA patients. Exercise participation increased muscle strength preoperatively (18% in THA patients and 20% in TKA patients), whereas the control patients had essentially no change in strength (P > 0.05 for exercise versus education in both THA and TKA groups). Exercise participation prior to total joint arthroplasty substantially reduced the risk of discharge to a rehabilitation facility in THA and TKA patients (adjusted odds ratio 0.27, 95% confidence interval 0.074–0.998). The intervention had no effects on outcomes 8 and 26 weeks postoperatively.

Conclusion

A 6‐week presurgical exercise program can safely improve preoperative functional status and muscle strength levels in persons undergoing THA. Additionally, exercise participation prior to total joint arthroplasty dramatically reduces the odds of inpatient rehabilitation.
Comment on the use of self‐reporting instruments to assess patients with rheumatoid arthritis: The longitudinal association between the DAS28 and the VAS general health
Authors: Kievit W. , Welsing P. M. J. , Adang E. M. M. , Eijsbouts A. M. , Krabbe P. F. M. , van Riel P. L. C. M.
Published: September 2006

Objective

Recently, the use of patient self‐reporting instruments instead of clinical, objective measurements to assess rheumatoid arthritis (RA) patients was proposed. This assumes a constant association between disease activity and the self‐reporting instruments. The objective was to explore the association (in time) between disease activity and patient perception of general health, disease activity, pain, and functional disability in patients with RA.

Methods

Data of 624 newly diagnosed RA patients who completed 3 years of followup were analyzed. Cross‐sectional linear regression models and longitudinal regression models were estimated, with a visual analog scale (VAS) measuring general health (VAS‐GH; 0 = best, 100 = worst) as a dependent variable and the Disease Activity Score (DAS28) without the VAS‐GH as an independent variable. Other dependent variables were VAS disease activity, pain, and the Health Assessment Questionnaire.

Results

The DAS28 and VAS‐GH were significantly associated in RA patients (P < 0.001). However, the explained variance was low (6.7%). From diagnosis to 3 years after the diagnosis, the intercept decreased given the same regression coefficient. The longitudinal regression model showed that the VAS‐GH improved during disease course independent of a change in DAS28. Analyses on the other outcome parameters showed similar results.

Conclusion

Patients' perception of health can be different with equal disease activity, depending on the moment in the disease course. Furthermore, our results indicate that self‐reported measures on functionality, disease activity, and general health cannot substitute for objective measures of disease activity in RA in longitudinal studies; subsequently, both need to be measured.
Myositis‐specific and myositis‐associated antibodies in a series of eighty‐eight mediterranean patients with idiopathic inflammatory myopathy
Authors: Selva‐O'Callaghan Albert , Labrador‐Horrillo Moisés , Solans‐Laque Roser , Simeon‐Aznar Carmen Pilar , Martínez‐Gómez Xavier , Vilardell‐Tarrés Miquel
Published: September 2006

Objective

To determine the prevalence of myositis‐specific autoantibodies (MSAs) and myositis‐associated autoantibodies (MAAs) and their clinical and immunogenetic correlations in Mediterranean patients with idiopathic inflammatory myopathies.

Methods

Sera from 88 patients were studied for MSAs and MAAs by RNA and protein immunoprecipitation. HLA typing was performed by sequence‐specific primer– and sequence‐specific oligonucleotide–polymerase chain reaction and serology. Statistical analyses were performed with Student's t‐test and Fisher's exact test. Cumulative survival probabilities were estimated by the Kaplan‐Meier method and Cox regression analysis.

Results

Twenty‐eight patients (30%) had MSAs, most commonly antisynthetase antibodies (23.9%). Six patients (7.5%) had anti–Mi‐2 antibodies. No anti–signal recognition particles were found. Arthritis, mechanic's hands, interstitial lung disease, and sicca syndrome were more prevalent in patients with antisynthetase antibodies. Dysphagia and the need for more treatment courses were more frequent in patients who were anti–Mi‐2 positive. Forty‐three patients (48%) had MAAs, 20 (22%) with anti–Ro 60 and 18 (20.4%) with anti–Ro 52. Ten patients (11.4%) were positive for anti–PM‐Scl, 6 (6.8%) for anti‐RNP, and 1 for anti‐Ku antibodies. Patients with PM‐Scl, RNP, or Ro antibodies were more often classified as having overlap syndrome. Immunogenetic studies found a significant association between HLA–DR3 and the presence of antisynthetase antibodies (P = 0.049), anti–PM‐Scl antibodies (P = 0.017), and interstitial lung disease (P = 0.03). No statistically significant differences in mortality, survival, or clinical course were observed between patients positive for MSAs or MAAs and the remaining patients.

Conclusion

These results are consistent with those from other published series, although some differences warrant consideration. Autoantibody studies may be useful for defining more homogeneous groups of patients with idiopathic inflammatory myopathies.
Beurteilung der Standsicherheit und Gebrauchstauglichkeit von dauerhaft rückverankerten Bauwerken
Authors: Hanel Jens , Prehn Wolfgang
Published: September 2006

Daueranker können naturgemäß nicht von außen begutachtet werden und sind trotzdem für die normgemäße Lebensdauer von bis zu 100 Jahren ausgelegt. In diesem Aufsatz wird von der Erfassung, Analyse und Bewertung von rückverankerten Bauwerken im Verantwortungsbereich des Landesbetriebs Straßenbau Nordrhein‐Westfalen (LS NRW) berichtet. Von 45 potentiell gefährdeten Bauwerken kann für 14 Bauwerke eine unmittelbare Gefährdung nicht ausgeschlossen werden. Die Analyse und Bewertung beruht dabei auf der Fragestellung, ob plötzliches Versagen möglich ist, obwohl alle äußeren Hinweise gegen eine Gefährdung der lokalen oder globalen Standsicherheit sprechen. Insbesondere Bauwerke, die in der zulassungslosen Zeit, also vor Inkrafttreten der DIN 4125‐11972 und 4125‐21976, hergestellt worden sind, können nicht per se als dauerhaft standsicher eingestuft werden. Ein Verfahren wird vorgestellt, wie aus einer vergleichsweise einfachen Betrachtung eine Gefährdung grundsätzlich ausgeschlossen werden kann.
Tragende Glasstützen für eine Café‐Bar in Göppingen
Authors: Pocanschi Adrian , Phocas Marios C.
Published: September 2006

Im vorliegenden Aufsatz werden Entwurf und Berechnungsansatz von zwei Glasstützen eines dreiseitig verglasten Bauwerks der Innenstadt von Göppingen aufgezeigt. Die Glasstützen sind zum ersten Mal in der Bundesrepublik Deutschland als tragende Bauteile realisiert worden. Sie bestehen aus jeweils einem Schwert und aus zwei Flügeln, die kreuzförmig daran angeschlossen sind. Beide Elemente bestehen aus Verbundsicherheitsglas, aus jeweils drei teilvorgespannten Scheiben. Nach einer kurzen baukonstruktiven Beschreibung werden die statischen Nachweise, der Tragfähigkeit der Stützen, der Resttragfähigkeit der Stützen und des Gesamttragwerks bei möglichen Schadensszenarien der Tragelemente, erläutert. Durch dieses Projekt wird die Anwendung von Glas für primäre Tragglieder vom Gebäude belegt.
Effects of naringin on the pharmacokinetics of intravenous paclitaxel in rats
Authors: Lim Sung‐Cil , Choi Jun‐Shik
Published: September 2006

It was reported that paclitaxel is an inhibitor of hepatic P‐glycoprotein (P‐gp) and hepatic microsomal cytochrome P450 (CYP) 3A1/2, and that naringin is an inhibitor of biliary P‐gp and CYP3A1/2 in rats. The purpose of this study was to report the effects of oral naringin on the pharmacokinetics of intravenous paclitaxel in rats. Oral naringin (3.3 and 10 mg/kg) was pretreated 30 min before intravenous (3 mg/kg) administration of paclitaxel. After intravenous administration of paclitaxel, the AUC was significantly greater (40.8% and 49.1% for naringin doses of 3.3 and 10 mg/kg, respectively), and Cl was significantly slower (29.0% and 33.0% decrease, respectively) than controls. The significantly greater AUC could be due mainly to an inhibition of metabolism of paclitaxel via CYP3A1/2 by oral naringin. The inhibition of hepatic P‐gp by oral naringin could also contribute to the significantly greater AUC of intravenous paclitaxel by oral naringin. Copyright © 2006 John Wiley & Sons, Ltd.
More than, less than, or minimum, maximum: how upper and lower bounds determine subjective interval estimates
Authors: Teigen Karl Halvor , Halberg Anne‐Marie , Fostervold Knut Inge
Published: September 2006

Uncertain quantities can be described by single‐point estimates of lower interval bounds (X1), upper interval bounds (X2), two‐bound estimates (separate estimates of X1 and X2), and by ranges (X1−X2). A price estimation task showed that single‐bound estimates phrased as “T costs more than X1” and “T costs less than X2,” yielded much larger intervals than “minimum X1” and “maximum X2.” This difference can be attributed to exclusive interpretations of X1 and X2 in the first case (X1 and X2 are unlikely values), and inclusive interpretations in the second (X1 and X2 are likely values). This pattern of results was replicated in other domains where participants estimated single targets. When they estimated a distribution of targets, the pattern was reversed. “Minimum” and “maximum” values of variable quantities (e.g., flight prices) were found to delimit larger intervals than “more than” and “less than” estimates. Copyright © 2006 John Wiley & Sons, Ltd.
Expression of bacterial biphenyl‐chlorobiphenyl dioxygenase genes in tobacco plants
Authors: Mohammadi Mahmood , Chalavi Vida , Novakova‐Sura Martina , Laliberté Jean‐François , Sylvestre Michel
Published: September 2006

Optimized plant–microbe bioremediation processes in which the plant initiates the metabolism of xenobiotics and releases the metabolites in the rhizosphere to be further degraded by the rhizobacteria is a promising alternative to restore contaminated sites in situ. However, such processes require that plants produce the metabolites that bacteria can readily oxidize. The biphenyl dioxygenase is the first enzyme of the bacterial catabolic pathway involved in the degradation of polychlorinated biphenyls. This enzyme consists of three components: the two sub‐unit oxygenase (BphAE) containing a Rieske‐type iron–sulfur cluster and a mononuclear iron center, the Rieske‐type ferredoxin (BphF), and the FAD‐containing ferredoxin reductase (BphG). In this work, based on analyses with Nicotiana benthamiana plants transiently expressing the biphenyl dioxygenase genes from Burkholderia xenovorans LB400 and transgenic Nicotiana tabacum plants transformed with each of these four genes, we have shown that each of the three biphenyl dioxygenase components can be produced individually as active protein in tobacco plants. Therefore, when BphAE, BphF, and BphG purified from plant were used to catalyze the oxygenation of 4‐chlorobiphenyl, detectable amounts of 2,3‐dihydro‐2, 3‐dihydroxy‐4′‐chlorobiphenyl were produced. This suggests that creating transgenic plants expressing simultaneously all four genes required to produce active biphenyl dioxygenase is feasible. Biotechnol. Bioeng. 2007;97: 496–505. © 2006 Wiley Periodicals, Inc.