bluuebunny/crossref_metadata_2025 huggingface dataset:
DNA fingerprinting tags novel altered chromosomal regions and identifies the involvement of SOX5 in the progression of prostate cancer
Authors: Ma Stephanie , Chan Yuen Piu , Woolcock Bruce , Hu Liang , Wong Kai Yau , Ling Ming Tat , Bainbridge Terry , Webber Douglas , Chan Tim Hon Man , Guan Xin‐Yuan , Lam Wan , Vielkind Juergen , Chan Kwok Wah
Published: December 2008

Identification of genomic alterations associated with the progression of prostate cancer may facilitate the better understanding of the development of this highly variable disease. Matched normal, premalignant high‐grade prostatic intraepithelial neoplasia and invasive prostate carcinoma cells were procured by laser capture microdissection (LCM) from human radical prostatectomy specimens. From these cells, comparative DNA fingerprints were generated by a modified PCR‐based technique called scanning of microdissected archival lesion (SMAL)‐PCR. Recurrent polymorphic fingerprint fragments were used in tagging altered chromosomal regions. Altered regions were found at cytobands 1p31.3, 1q44, 2p23.1, 3p26.3, 3q22.3, 4q22.3, 4q35.2, 5q23.2, 8q22.3, 8q24.13, 9q21.3, 9q22.32, 10q11.21, 11p13, 12p12.1, 13q12.1, 16q12.2 and 18q21.31. Candidate genes in the surrounding area that may possibly harbor mutations that change normal prostatic cells to progress into their tumor stages were proposed. Of these fragments, a 420 bp alteration, absent in all 26 normal samples screened, was observed in 2 tumors. This fragment was cloned, sequenced and localized to chromosome 12p12.1. Within this region, candidate gene sex determining region Y‐box 5 (SOX5) was proposed. Further studies of SOX5 in cell lines, xenografts and human prostate specimens, at both the RNA and protein levels, found overexpression of the gene in tumors. This overexpression was then subsequently found by fluorescent in situ hybridization to be caused by amplification of the region. In conclusion, our results suggest LCM coupled with SMAL‐PCR DNA fingerprinting is a useful method for the screening and identification of chromosomal regions and genes associated with cancer development. Further, overexpression of SOX5 is associated with prostate tumor progression and early development of distant metastasis. © 2008 Wiley‐Liss, Inc.
Immunoglobulin subclass levels in patients with non‐Hodgkin lymphoma
Authors: Biggar Robert J. , Christiansen Michael , Rostgaard Klaus , Smedby Karin Ekström , Adami Hans‐Olov , Glimelius Bengt , Hjalgrim Henrik , Melbye Mads
Published: December 2008

Allergy/atopy has been suggested to protect against non‐Hodgkin lymphoma (NHL) and specific IgE levels are decreased in patients with NHL. We speculated that all immunoglobulin subclass levels might be downregulated in NHL and examined levels of IgM, IgD, IgA, IgE, IgG and IgG4 in 200 NHL patients and 200 age‐ and sex‐matched controls. Patients with B‐cell NHL of many types had consistently lower median immunoglobulin subclass levels than controls. In every subclass except IgD, about 10–15% of B‐cell NHL patients had absolute levels below the 2.5 percentile of controls. Subclass levels correlated with each other and many patients had more than one significantly low level. Levels were lowest for IgG4 and IgE. Patients with chronic lymphocytic leukemia/small lymphocytic lymphoma had especially low total IgE levels. In other B‐cell NHL types, total IgE levels were decreased to a similar extent as other immunoglobulin subclasses. In conclusion, low IgE levels are only part of a more generalized loss of immunoglobulins of all subtypes in a wide variety of B‐cell NHL types. Low immunoglobulin levels appear to be a consequence of B‐cell NHL presence, and we speculate about molecular mechanisms that could reduce all immunoglobulin subclasses in B‐cell NHL. © 2008 Wiley‐Liss, Inc.
Diet and upper‐aerodigestive tract cancer in Europe: The ARCAGE study
Authors: Lagiou Pagona , Talamini Renato , Samoli Evangelia , Lagiou Areti , Ahrens Wolfgang , Pohlabeln Hermann , Benhamou Simone , Bouchardy Christine , Slamova Alena , Schejbalova Miriam , Merletti Franco , Richiardi Lorenzo , Kjaerheim Kristina , Agudo Antonio , Castellsague Xavier , Macfarlane Tatiana V. , Macfarlane Gary J. , Biggs Anne‐Marie , Barzan Luigi , Canova Cristina , Simonato Lorenzo , Lowry Raymond J. , Conway David I. , McKinney Patricia A. , Znaor Ariana , McCartan Bernard E. , Healy Claire M. , Marron Manuela , Hashibe Mia , Brennan Paul
Published: December 2008

There is suggestive, but inconclusive, evidence that dietary factors may affect risk of cancers of the upper aerodigestive tract (UADT). In the context of the alcohol‐related cancers and genetic susceptibility in Europe study, we have examined the association of dietary factors with UADT cancer risk. We have analyzed data from 2,304 patients with UADT cancer and 2,227 control subjects recruited in 14 centers in 10 European countries. Dietary data were collected through a semi‐quantitative food frequency questionnaire that also assessed preferred temperature of hot beverages. Statistical analyses were conducted through multiple logistic regression controlling for potential confounding variables, including alcohol intake and smoking habits. Consumption of red meat (OR per increasing tertile = 1.14, 95% CI: 1.05–1.25), but not poultry, was significantly associated with increased UADT cancer risk and the association was somewhat stronger for esophageal cancer. Consumption of fruits (OR per increasing tertile = 0.68, 95% CI: 0.62–0.75) and vegetables (OR per increasing tertile = 0.73, 95% CI: 0.66–0.81) as well as of olive oil (OR for above versus below median = 0.78, 95% CI 0.67–0.90) and tea (OR for above versus below median = 0.83, 95% CI 0.69–0.98) were significantly associated with reduced risk of UADT cancer. There was no indication that an increase in tea or coffee temperature was associated with increased risk of UADT overall or cancer of the esophagus; in fact, the association was, if anything, inverse. In conclusion, the results of this large multicentric study indicate that diet plays an important role in the etiology of UADT cancer. © 2008 Wiley‐Liss, Inc.
Preoperative chemoradiation versus radiation alone for stage II and III resectable rectal cancer: A systematic review and meta‐analysis
Authors: Ceelen Wim , Fierens Kjell , Van Nieuwenhove Yves , Pattyn Piet
Published: December 2008

Combining chemotherapy with preoperative radiotherapy (RT) has a sound radiobiological rationale. We performed a systematic review and meta‐analysis of trials comparing preoperative RT with preoperative chemoradiation (CRT) in rectal cancer patients. The Cochrane Central Register of Controlled Trials, Web of Science, Embase and Medline (Pubmed) were searched from 1975 until June 2007. Dichotomous parameters were summarized using the odds ratio while time to event data were analyzed using the pooled hazard ratio for death. From the primary search result of 324 trials, 4 relevant randomized trials were identified. The addition of chemotherapy significantly increased grade III and IV acute toxicity (p = 0.002) while no differences were observed in postoperative morbidity or mortality. Preoperative CRT significantly increased the rate of pathological complete response (p < 0.001) although this did not translate into a higher sphincter preservation rate (p = 0.29). The local recurrence rate was significantly lower in the CRT group (p < 0.001). No statistically significant differences were observed in disease free survival (p = 0.89) or overall survival (p = 0.79). Compared to preoperative RT alone, preoperative CRT improves local control in rectal cancer but is associated with a more pronounced treatment related toxicity. The addition of chemotherapy does not benefit sphincter preservation rate or long‐term survival. Future trials should address improvements in the rate of distant metastasis and overall survival by incorporating more active chemotherapy. © 2008 UICC
Reproductive factors, exogenous hormone use and risk of lymphoid neoplasms among women in the National Institutes of Health‐AARP Diet and Health Study Cohort
Authors: Morton Lindsay M. , Wang Sophia S. , Richesson Douglas A. , Schatzkin Arthur , Hollenbeck Albert R. , Lacey James V.
Published: December 2008

Reasons for higher incidence of lymphoid neoplasms among men than women are unknown. Because female sex hormones have immunomodulatory effects, reproductive factors and exogenous hormone use may affect risk for lymphoid malignancies. Previous epidemiologic studies on this topic have yielded conflicting results. Within the National Institutes of Health‐AARP Diet and Health Study cohort, we prospectively analyzed detailed, questionnaire‐derived information on menstrual and reproductive factors and use of oral contraceptives and menopausal hormone therapy among 134,074 US women. Using multivariable proportional hazards regression models, we estimated relative risks (RRs) for 85 plasma cell neoplasms and 417 non‐Hodgkin lymphomas (NHLs) identified during follow‐up from 1996 to 2002. We observed no statistically significant associations between plasma cell neoplasms, NHL, or the 3 most common NHL subtypes and age at menarche, parity, age at first birth, oral contraceptive use or menopausal status at baseline. For menopausal hormone therapy use, overall associations between NHL and unopposed estrogen and estrogen plus progestin were null, with the potential exception of an inverse association (RR = 0.49, 95% CI, 0.25–0.96) between use of unopposed estrogen and diffuse large B‐cell lymphoma (DLBCL), the most common NHL subtype, among women with a hysterectomy. These data do not support an important role for reproductive factors or exogenous hormones in modulating lymphomagenesis. © 2008 Wiley‐Liss, Inc.
Epidermal growth factor receptor gene mutations in papillary thyroid carcinoma
Authors: Masago Katsuhiro , Asato Ryo , Fujita Shiro , Hirano Shigeru , Tamura Yoshihiro , Kanda Tomoko , Mio Tadashi , Katakami Nobuyuki , Mishima Michiaki , Ito Juichi
Published: December 2008

Recent studies have indicated that somatic mutations in the epidermal growth factor receptor (EGFR) gene have been identified in a subset of patients with nonsmall‐cell lung cancer (NSCLC) and are associated with sensitivity to the EGFR‐tyrosine‐kinase inhibitors. These mutations have been reported to be almost exclusively found in a pulmonary adenocarcinoma subgroup of NSCLC, with a low frequency in other solid tumors. We describe a patient with advanced‐stage papillary thyroid carcinoma (PTC) whose disease had been diagnosed as pulmonary adenocarcinoma at first, and who had a marked response to the EGFR‐tyrosine‐kinase inhibitor, gefitinib. An in‐frame deletion in exon 19 that eliminated 4 amino acids at positions 746 through 750, which is one of the common drug‐sensitive mutations in pulmonary adenocarcinoma, and a serine‐to‐proline substitution at codon 752, were found in a tumor specimen of the patient. We subsequently searched for mutations in the EGFR tyrosine kinase domain in primary tumors from 23 patients with PTC, and drug‐sensitive mutations commonly observed in pulmonary adenocarcinoma were found in 7 of these patients. Our observation of a high frequency of the EGFR‐activating mutations in PTC suggests that the EGFR mutation may be an important event in the development of PTC. EGFR gene amplification, also considered to be a predictor of response to EGFR‐tyrosine‐kinase inhibitors, was evaluated by fluorescence in situ hybridization (FISH); however, only 1 FISH‐positive tumor was detected. Our data suggest that EGFR‐tyrosine‐kinase inhibitors may deserve consideration in the treatment of a subset of patients with PTC, just as with pulmonary adenocarcinoma. © 2008 Wiley‐Liss, Inc.
Injectable cell‐free template for bone‐tissue formation
Authors: Bergman Kristoffer , Engstrand Thomas , Hilborn Jöns , Ossipov Dmitri , Piskounova Sonya , Bowden Tim
Published: December 2008

Here we present a novel injectable hydrogel which forms a template for de novo formation of bone tissue. Hydrogel formation takes place in situ in less than 1 min by the cross‐linking of multifunctional hyaluronic acid and polyvinyl alcohol derivatives. Endogenous cells are recruited in vivo by incorporating bone morphogenetic protein‐2 (BMP‐2), a powerful promoter for osteogenic differentiation. The hydrogel was evaluated in vitro by performing a cell viability test and a release study and in vivo by a rat ectopic model. Examination by X‐ray, microcomputed tomography, and histology revealed a significant bone formation at the target site for gels containing BMP‐2, and a complete degradation was observed for gels without BMP‐2 four weeks after injection. There were no signs of inflammation or foreign body response in either group and we believe that this system has the potential as an off‐the‐shelf injectable to be used where bone tissue is needed. © 2008 Wiley Periodicals, Inc. J Biomed Mater Res, 2009
Biological evaluation of a novel chitosan‐PVA‐based local delivery system for treatment of periodontitis
Authors: Wang Ling Chong , Wu Hao , Chen Xi Guang , De Li Li , Ji Qiu Xia , Liu Cheng Sheng , Yu Le Jun , Ran Chao , Zhao Qing Sheng
Published: December 2008

In the study, we intend to design a suitable localized drug delivery system (LDDS) with chitosan and poly vinyl alcohol (PVA) for treating serve periodontitis. For that, a novel formulation based on the incorporation of chitosan‐based microspheres into PVA film was prepared. As the core parts of the novel formulation, chitosan‐based microspheres were prepared form chitosan and/or carboxymethyl‐chitosan (CM‐chitosan) by using water‐in‐oil emulsification method. Then basic in vitro and in vivo experiments focusing on biocompatibility and biodegradability of the two chitosan‐based microspheres were carried out to evaluate the feasibility of the novel LDDS. In vitro tests, besides having no hemolysis, chitosan microsphere (Cs1‐Ms), and CM‐chitosan microsphere (Cs2‐Ms) have adsorbed little proteins on their surfaces. Moreover, plasma proteins adsorbed on Cs2‐Ms, most of which can easily desorbed, are much less than that adsorbed on Cs1‐Ms. This indicates that Cs2‐Ms perhaps has better biocompatibility than Cs1‐Ms. In vivo tests, Cs1‐Ms and Cs2‐Ms were subcutaneously implanted in rat to investigate the host tissue inflammatory response. Implantations of Cs1‐Ms and Cs2‐Ms induced a little more severe inflammation when compared with the implantation of PVA film. However, the difference on in vivo biocompatibility between Cs1‐Ms and Cs2‐Ms could not be confirmed by the implantation model of our experiments. Both Cs1‐Ms and Cs2‐Ms had suffered bioerosion when they were subcutaneously implanted. The hard and compact matrixes of Cs1‐Ms were degraded very slowly, and only some trifling degradation had been found until 4 weeks of implantation. In contrast, Cs2‐Ms is soft and more hydrophilic, and can be quickly degraded in a form of diffluence by the physiological circumstance. All these results suggested that Cs2‐Ms had better potentials used as core parts of the novel designed LDDS in the future developments. © 2008 Wiley Periodicals, Inc. J Biomed Mater Res, 2009
Synthesis and characterization of recombinant factor VIIa‐conjugated magnetic iron oxide nanoparticles for hemophilia treatment
Authors: Shafir Gilead , Galperin Anna , Margel Shlomo
Published: December 2008

Maghemite (γ‐Fe2O3) nanoparticles of 15.0 ± 2.1 nm in diameter were prepared by nucleation, followed by controlled growth of magnetic iron oxide thin films onto gelatin nuclei. Functionalization of these magnetic nanoparticles with activated double bonds was accomplished by interacting divinyl sulfone with the gelatin coating of the γ‐Fe2O3 nanoparticles. The activated double bonds were then used for covalent binding, via Michael addition reaction, of recombinant factor VIIa and human serum albumin to the surface of these nanoparticles. Recombinant factor VIIa was also physically bound to the magnetic nanoparticles by interacting this factor with the human serum albumin conjugated γ‐Fe2O3 nanoparticles. The influence of factor VIIa concentration on the immobilization yield has been elucidated. Leakage of the bound factor VIIa into PBS containing 4% albumin was insignificant. The coagulant activity of the physically adsorbed recombinant factor VIIa was similar to that of the free one and was significantly better than that of the covalently bound. The blood half‐life of free factor VIIa is short, about 2–3 h, because of digestion by proteolytic enzymes and inhibitory effects. Stabilization of factor VIIa against trypsin (a model proteolytic enzyme) and chloromethyl ketone‐type inhibitor was accomplished by conjugation of the factor to the γ‐Fe2O3 nanoparticles. This stabilization may extend the blood half‐life of factor VIIa. Therefore, IV injection of factor VIIa conjugated γ‐Fe2O3 nanoparticles instead of free factor may avoid the frequent dosing and reduce the cost of hemophilia treatment. © 2008 Wiley Periodicals, Inc. J Biomed Mater Res, 2009
In vitro biocompatibility of hydroxyapatite‐reinforced polymeric composites manufactured by selective laser sintering
Authors: Zhang Y. , Hao L. , Savalani M. M. , Harris R. A. , Di Silvio L. , Tanner K. E.
Published: December 2008

The selective laser sintering (SLS) technique was used to manufacture hydroxyapatite‐reinforced polyethylene and polyamide composites as potential customized maxillofacial implants. In vitro tests were carried out to assess cellular responses, in terms of cell attachment, morphology, proliferation, differentiation, and mineralized nodule formation, using primary human osteoblast cells. This study showed that the SLS composite processed was biocompatible, with no adverse effects observed on cell viability and metabolic activity, supporting a normal metabolism and growth pattern for osteoblasts. Positive von Kossa staining demonstrated the presence of bone‐like mineral on the SLS materials. Higher hydroxyapatite content composites enhanced cell proliferation, increased alkaline phosphatase activity, and produced more osteocalcin. The present findings showed that SLS materials have good in vitro biocompatibility and hence demonstrated biologically the potential of SLS for medical applications. © 2008 Wiley Periodicals, Inc. J Biomed Mater Res, 2009
In vitro and in vivo degradation of poly(1,3‐diamino‐2‐hydroxypropane‐co‐polyol sebacate) elastomers
Authors: Bettinger Christopher J. , Bruggeman Joost P. , Borenstein Jeffrey T. , Langer Robert
Published: December 2008

Biomaterials with a wide range of tunable properties are desirable for application‐specific purposes. We have previously developed a class of elastomeric poly(ester amides) based on the amine alcohol 1,3‐diamino‐2‐hydroxypropane termed poly(1,3‐diamino‐2‐hydroxypropane‐co‐polyol sebacate) or APS. In this work, we have synthesized and characterized formulations of APS polymers and studied the degradation of these polymers in vitro and in vivo. It was found that the chemical, physical, and mechanical properties of APS polymers could be tuned by adjusting monomer feed ratios and polymerization conditions. The degradation kinetics could also be greatly influenced by altering the formulation of APS polymers. In vivo degradation half‐lives ranged from 6 to ∼100 weeks. Furthermore, the dominant degradation mechanism (i.e. hydrolytic or enzymatic) could be controlled by adjusting the specific formulation of the APS polymer. On the basis of the observed in vitro and in vivo biodegradation phenomena, we also propose that the primary modes of degradation are composition dependent. © 2008 Wiley Periodicals, Inc. J Biomed Mater Res, 2009
Nanomechanical properties of calcification, fibrous tissue, and hematoma from atherosclerotic plaques
Authors: Ebenstein Donna M. , Coughlin Dezba , Chapman Joan , Li Cheng , Pruitt Lisa A.
Published: December 2008

Clinical events such as heart attack and stroke can be caused by the rupture of atherosclerotic plaques in artery walls. Computational modeling is often used to better understand atherosclerotic disease progression to identify “vulnerable” plaques (i.e., those likely to rupture) and to tailor treatments according to tissue composition. However, because of the heterogeneity of plaque tissue, there are limited data available on the material properties of individual plaque constituents. The goal of this study was to use nanoindentation to measure the mechanical properties of blood clots, fibrous tissue, partially calcified fibrous tissue, and bulk calcifications from human atherosclerotic plaque tissue. Fourier transform infrared (FTIR) spectroscopy was used to quantify the amount of mineral and lipid in each tissue region tested. The results demonstrate that the stiffness of plaque tissue increases with increasing mineral content. In addition, by providing the first experimental data on atherosclerotic calcifications, these data show that some of the estimated modulus values commonly used in computational models greatly underestimate the stiffness of the fully calcified tissue. © 2008 Wiley Periodicals, Inc. J Biomed Mater Res, 2009
Degradation behavior of poly(glycerol sebacate)
Authors: Pomerantseva Irina , Krebs Nicholas , Hart Alison , Neville Craig M. , Huang Albert Y. , Sundback Cathryn A.
Published: December 2008

Poly(glycerol sebacate) (PGS), a promising scaffold material for soft tissue engineering applications, is a soft, tough elastomer with excellent biocompatibility. However, the rapid in vivo degradation rate of PGS limits its use as a scaffold material. To determine the impact of crosslink density on degradation rate, a family of PGS materials was synthesized by incrementally increasing the curing time from 42 to 144 h, at 120°C and 10 mTorr vacuum. As expected, PGS became a stiffer, tougher, and stronger elastomer with increasing curing time. PGS disks were subcutaneously implanted into rats and periodically harvested; only mild tissue responses were observed and the biocompatibility remained excellent. Regardless of crosslink density, surface erosion degradation was observed. The sample dimensions linearly decreased with implantation time, and the mass loss rates were constant after 1‐week implantation. As surface erosion degradation frequently correlates with enzymatic digestion, parallel in vitro digestion studies were conducted in lipase solutions which hydrolyze ester bonds. Enzymatic digestion played a significant role in degrading PGS, and the mass loss rates were not a function of curing time. Alternative chemistry approaches will be required to decrease the enzymatic hydrolysis rate of the ester bonds in PGS polymers. © 2008 Wiley Periodicals, Inc. J Biomed Mater Res, 2009
Polar surface chemistry of nanofibrous polyurethane scaffold affects annulus fibrosus cell attachment and early matrix accumulation
Authors: Yang Liu , Kandel Rita A. , Chang Godfrey , Santerre J. Paul
Published: December 2008

Regeneration of the annulus fibrosus (AF), one of the three components of the intervertebral disc (IVD), is challenging because of the tissue complexity and our limited knowledge about AF cell biology. The purpose of this study was to determine if modulating surface chemistry of polycarbonate polyurethane (PU) scaffolds would influence annulus fibrosus cell adhesion and early tissue formation. To vary surface energy, a novel anionic dihydroxyl oligomer (ADO) was synthesized and incorporated into the PU base polymer at three different concentrations [0.05, 0.5, and 5% (wt %)]. The polymeric materials were fabricated into nanoscale fibrous scaffolds using electrospinning. PU nanofibrous scaffolds in the absence or presence of different amounts of ADO were similar in appearance. Surface energy was significantly enhanced with increasing ADO content, as indicated by the decreasing water contact angle measurements. Increasing the material surface's polar character for the scaffolds resulted in a positive enhancement of AF cell attachment. The mechanism of this effect was complex as at higher ADO concentrations, increased cell adhesion was mediated by both serum and newly synthesized proteins, whereas at low ADO concentrations the latter had minimal effect. Collagen but not proteoglycan accumulation was also modulated by increasing ADO content. This study demonstrated that nanoscale fibrous PU scaffolds containing ADO may be appropriate candidates in the formation of tissue engineered annulus fibrosus tissue, and that material surface polar character can be used to influence AF cell attachment and collagen accumulation. © 2008 Wiley Periodicals, Inc. J Biomed Mater Res, 2009
In vivo study effect of particulate Bioglass® in the prevention of infection in open fracture fixation
Authors: Xie Zong‐Ping , Zhang Chang‐Qing , Yi Cheng‐Qing , Qiu Jian‐Jun , Wang Jian‐Qiang , Zhou Juan
Published: December 2008

There are many in vitro experiments showing that particulate bioactive glasses have a broad and certain antibacterial effect, but there is no report about this antibacterial effect in vivo so far. The aim of this study is to examine the efficacy of particulate Bioglass® in reducing the rate of infection with Staphylococcus aureus after the fixation of open tibial fractures in rabbits. The test in vivo was carried out with male rabbits split into two groups infected with Staphylococcus aureus at the right tibial fracture sites fixed with plate and screw, either with or without bioactive glass respectively. Culture results show that six of ten rabbits from the control group had a positive culture for the strain of Staphylococcus aureus ATCC25923, compared with six of the nine rabbits from the Bioglass® group. The median radiographic score is 4.5 points for the rabbits from the control group and 4 points for the rabbits from the Bioglass® group. The median histopathological score was 2.5 points for the rabbits in the control group and 3 points for the rabbits in the Bioglass® group. In conclusion, this study showed no significant difference between the rates of infection of two groups. Particulate Bioglass® did not reduce the rate of infection with Staphylococcus aureus after the fixation of open tibial fractures in rabbits. © 2008 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2009
Adhesion of amorphous calcium phosphate composites bonded to dentin: A study in failure modality
Authors: O'Donnell Justin N. R. , Schumacher Gary E. , Antonucci Joseph M. , Skrtic Drago
Published: December 2008

Aims:

As a bioactive filler capable of remineralizing tooth structures, the main disadvantage of as‐made amorphous calcium phosphate (am‐ACP) are its large agglomerates. The objective of this study was to mill ACP, and compare the adhesive strength with dentin, work to fracture, and failure modes of both groups to glass‐filled composites and one commercial compomer after 24 h, 1 week, 1, 3, and 6 months of exposure to simulated saliva solution (SLS). Flat dentin surfaces were acid‐etched, primed, and photopolymerized. Composites were applied, photo‐cured, and debonded in shear. The resin used in each composite was identical: ethoxylated bisphenol A dimethacrylate, triethylene glycol dimethacrylate, 2‐hydroxyethyl methacrylate, and methacryloxyethyl phthalate. Fillers consisted of am‐ACP and milled ACP (m‐ACP), and a strontium‐containing glass (Sr‐glass) at respective mass fractions of (40, 60, and 75%).

Findings:

Ninety percent of the fracture surfaces in this study showed adhesive failure, with most of these occurring at the dentin/primer interface. Fifty‐two percent of failures after 24‐h immersion occurred at the primer/composite interface. After 6 months of SLS exposure, 80% of specimens failed at the dentin/primer interface, with a 42% overall reduction in bond strength.

Conclusions:

Milled ACP composites showed initial mechanical advantages over am‐ACP composites and the compomer, and produced a higher incidence of a failure mode consistent with stronger adhesion. Evidence is provided which suggests that milled ACP composites may offer enhanced potential in clinical bonding applications. © 2008 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2009
Accelerated aqueous aging simulation of in vivo oxidation for gamma‐sterilized UHMWPE
Authors: Kurtz Steven M. , Siskey Ryan L. , Dumbleton John
Published: December 2008

In vivo oxidation of gamma air‐sterilized ultrahigh‐molecular‐weight polyethylene (UHMWPE) has been observed when joint replacement hip and knee components are explanted during revision surgery. The purpose of the present study was to extend a previously published accelerated aging protocol for gamma‐sterilized UHMWPE. Unsterilized and gamma‐sterilized GUR 1150 resin samples were aged in phosphate‐buffered saline (PBS) at 40 or 50°C for up to 52 weeks. Under these conditions, slower changes in oxidation index (OI) occurred than those previously observed by aging at 60°C. Reduction of aging temperature below 60°C also changed the kinetics of oxidation such that the aldehyde peak (1732 cm−1) present at higher temperature was eliminated making the ketone/carboxylic acid region (1713–1718 cm−1) the primary region contributing to the calculation of the OIs for each group. The oxidation profiles obtained after 52 weeks at 40 and 50°C were consistent with retrievals that have undergone low oxidation, associated with maximum OI values of less than 1. Aging at 50°C represents a compromise between the slower oxidation rate of in vivo temperatures and the nonphysiological kinetics of elevated temperatures in an aqueous environment. However, even at 50°C over a year of in vitro aqueous aging will be necessary to reproduce the oxidation levels observed in long‐term implanted acetabular retrievals. © 2008 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2009
Rietveld structure and in vitro analysis on the influence of magnesium in biphasic (hydroxyapatite and β‐tricalcium phosphate) mixtures
Authors: Kannan S. , Goetz‐Neunhoeffer F. , Neubauer J. , Rebelo A.H.S. , Valério P. , Ferreira J.M.F.
Published: December 2008

The structure of two different Mg‐substituted biphasic (HAP and β‐TCP) mixtures along with the biphasic mixtures without substituted Mg2+ was investigated using Rietveld refinement technique. The substituted Mg2+ was found in the β‐TCP phase and its influence on the composition has led to an increase in HAP content of Mg‐containing biphasic mixtures when compared with the HAP content detected in pure biphasic mixtures. The refined structural parameters of Ca10(PO4)6(OH)2 and β‐Ca3(PO4)2 confirmed that all the investigated compositions have crystallized in the corresponding hexagonal (space group P63/m) and rhombohedral (space group R3c) structures. The substitution of lower sized magnesium was found preferentially incorporated at the sixfold‐coordinated Ca (5) site of β‐TCP, which is due to the strong Ca (5)·O interaction among all the five different Ca sites of β‐Ca3(PO4)2. The in vitro tests using primary culture of osteoblasts showed that all the tested samples are biocompatible and promising materials for in vivo studies. © 2008 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2009
Faster and stronger vascular “Biotube” graft fabrication in vivo using a novel nicotine‐containing mold
Authors: Sakai Osamu , Kanda Keiichi , Takamizawa Keiichi , Sato Takayuki , Yaku Hitoshi , Nakayama Yasuhide
Published: December 2008

To accelerate the fabrication of in vivo‐tissue engineered autologous vascular prosthetic tissues, the “Biotube,” a novel drug‐coating mold was designed. The mold was prepared by impregnating nicotine as a model drug into a gelatinous matrix coated on acrylate rods (diameter, 2 mm; length, 20 mm). Upon embedding the molds into dorsal subcutaneous pouches of rats, completely encapsulated Biotubes with significant tissue migration accompanied by rich angiogenesis and having 3.8 times as many neovessels as the uncoated controls, were formed at only 2 weeks. The wall thickness and burst strength of the Biotubes were 399.9 ± 135.2 μm and 2682.6 ± 722.6 mmHg, respectively. These values were, respectively, more than 9.6 and 3.2 times greater than the corresponding controls. Therefore, it is confidently expected that the mechanical properties of Biotubes obtained by nicotine coating make them suitable for application as vascular grafts. © 2008 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2009
Comparison of the osteoblast and myoblast behavior on hydroxyapatite microgrooves
Authors: Lu Xiong , Leng Yang
Published: December 2008

Surface topography is one of the most important surface properties of biomaterials and microfabrication techniques provide new routes to produce precisely controlled surface topographies for investigating the topographic effects on cell behavior. In this study, hydroxyapatite (HA) microgrooved surfaces were used to study the osteoblast and myoblast response to the surface micro‐features. The microgrooves were first produced on silicon wafers by photolithography, and then coated with HA using sputtering technique. Orientation angle (OA) was used to evaluate the contact guidance introduced by microgrooves and form index (FI) was introduced to describe the cell morphology change. The results show that the microgroove effects on myoblasts are more obvious than those on osteoblasts, and the two types of cells are sensitive to different sizes of microgrooves. The microgrooves with 8 μm width strongly affect both osteoblasts and myoblasts, while the microgrooves with 24 μm width strongly affect myoblasts only. These results confirm that the surface topographic effect is of cell specific, and therefore, design of surface topographic features must be different for myoblasts and osteoblasts. © 2008 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2009
Endogenous FGF‐2 is critically important in PTH anabolic effects on bone
Authors: Sabbieti Maria Giovanna , Agas Dimitrios , Xiao Liping , Marchetti Luigi , Coffin J. Douglas , Doetschman Thomas , Hurley Marja M.
Published: December 2008

Parathyroid hormone (PTH) increases fibroblast growth factor receptor‐1 (FGFR1) and fibroblast growth factor‐2 (FGF‐2) expression in osteoblasts and the anabolic response to PTH is reduced in Fgf2−/− mice. This study examined whether candidate factors implicated in the anabolic response to PTH were modulated in Fgf2−/− osteoblasts. PTH increased Runx‐2 protein expression in Fgf2+/+ but not Fgf2−/− osteoblasts. By immunocytochemistry, PTH treatment induced nuclear accumulation of Runx‐2 only in Fgf2+/+ osteoblasts. PTH and FGF‐2 regulate Runx‐2 via activation of the cAMP response element binding proteins (CREBs). Western blot time course studies showed that PTH increased phospho‐CREB within 15 min that was sustained for 24 h in Fgf2+/+ but had no effect in Fgf2−/− osteoblasts. Silencing of FGF‐2 in Fgf2+/+ osteoblasts blocked the stimulatory effect of PTH on Runx‐2 and CREBs phosphorylation. Studies of the effects of PTH on proteins involved in osteoblast precursor proliferation and apoptosis showed that PTH increased cyclinD1‐cdk4/6 protein in Fgf2+/+ but not Fgf2−/− osteoblasts. Interestingly, PTH increased the cell cycle inhibitor p21/waf1 in Fgf2−/− osteoblasts. PTH increased Bcl‐2/Bax protein ratio in Fgf2+/+ but not Fgf2−/− osteoblasts. In addition PTH increased cell viability in Fgf2+/+ but not Fgf2−/− osteoblasts. These data suggest that endogenous FGF‐2 is important in PTH effects on osteoblast proliferation, differentiation, and apoptosis. Reduced expression of these factors may contribute to the reduced anabolic response to PTH in the Fgf2−/− mice. Our results strongly indicate that the anabolic PTH effect is dependent in part on FGF‐2 expression. J. Cell. Physiol. 219: 143–151, 2009. © 2008 Wiley‐Liss, Inc.
Roles of focal adhesions and fibronectin‐mediated cohesion in proliferation of confluent fibroblasts
Authors: Tanaka Maya , Abe Tatsuya , Hara Yoshitaka
Published: December 2008

Multilayered fibroblast sheets have applications as cell transplants for tissue engineering. One way to increase their therapeutic efficacy is to increase cell numbers in a graft, but the factors influencing multilayered growth remain poorly understood. In this study, we investigated the roles of focal adhesion (FA) assembly and intercellular cohesion through fibronectin (FN) in the proliferation of normal human fibroblasts at confluence. Density‐dependent growth‐arrested fibroblasts resumed DNA synthesis when cultured in multilayer formation medium (MFM) containing transforming growth factor‐β1, ascorbic acid, and serum. This proliferation depended on α5β1‐integrin‐mediated cell‐FN‐cell interactions because blocking them with antibodies inhibited DNA synthesis. However, cell‐FN‐cell cohesion operated well regardless of exposure to MFM, judging from several parameters, including FN matrix deposition, activated β1 integrin expression, and stress fiber development. Density‐arrested cells formed few FAs at the cell center. Exposure of the cells to MFM induced the formation of vinculin‐, paxillin‐, and phosphotyrosine‐containing FAs throughout the ventral cell‐surface, indicating ROCK‐mediated actomyosin contractile force generation. When the assembly of FAs was inhibited with either the ROCK inhibitor Y‐27632 or the myosin II inhibitor blebbistatin, the up‐regulation of DNA synthesis by MFM was suppressed. The drugs did not impair FN matrix deposition, activated β1 integrin expression, and stress fiber development. Thus, these results indicate that the formation of FAs promotes the proliferation of confluent fibroblasts with the support of α5β1‐integrin‐mediated cell‐FN‐cell cohesion. The present findings provide insights into the rational design of high‐density fibroblast transplants. J. Cell. Physiol. 219: 194–201, 2009. © 2008 Wiley‐Liss, Inc.
Calcification or dedifferentiation: Requirement to lock mesenchymal stem cells in a desired differentiation stage
Authors: Dickhut Andrea , Pelttari Karoliina , Janicki Patricia , Wagner Wolfgang , Eckstein Volker , Egermann Marcus , Richter Wiltrud
Published: December 2008

A current challenge in mesenchymal stem cell (MSC)‐based cartilage repair is to solve donor and tissue‐dependent variability of MSC cultures and to prevent chondrogenic cells from terminal differentiation like in the growth plate. The aim of this study was to select the best source for MSC which could promise stable cartilage formation in the absence of hypertrophy and ectopic in vivo mineralization. We hypothesized that MSC from synovium are superior to bone marrow‐ and adipose tissue‐derived MSC since they are derived from a joint tissue. MSC were characterized by flow cytometry. MSC pellets were cultured under chondrogenic conditions and differentiation was evaluated by histology, gene expression analysis, and determination of alkaline phosphatase activity (ALP). After chondrogenic induction, pellets were transplanted subcutaneously into SCID mice. MSC from bone marrow, adipose tissue, and synovium revealed similar COL2A1/COL10A1 mRNA levels after chondrogenic induction and were positive for collagen‐type‐X. Bone marrow‐derived and adipose tissue‐derived MSC showed significantly higher ALP activity than MSC from synovium. Low ALP‐activity before transplantation of pellets correlated with marginal calcification of explants. Surprisingly, non‐mineralizing transplants specifically lost their collagen‐type II, but not collagen‐type I deposition in vivo, or were fully degraded. In conclusion, the lower donor‐dependent ALP activation and reduced mineralization of synovium‐derived heterotopic transplants did not lead to stable ectopic cartilage as known from articular chondrocytes, but correlated with fibrous dedifferentation or complete degeneration of MSC pellets. This emphasizes that beside appropriate induction of differentiation, locking of MSC in the desired differentiation state is a major challenge for MSC‐based repair strategies. J. Cell. Physiol. 219: 219–226, 2009. © 2008 Wiley‐Liss, Inc.
Prenatal sonographic appearance of truncus arteriosus on wide‐band Doppler imaging
Authors: Hidaka Nobuhiro , Anami Ai , Yoshitomi Tomoyuki , Tsukimori Kiyomi , Wake Norio
Published: December 2008

Persistent truncus arteriosus is an uncommon congenital cardiac anomaly. In most patients, this condition is not diagnosed prior to birth. We report a case in which this uncommon cardiac anomaly was diagnosed prenatally using wide‐band Doppler imaging. When diagnosing fetal truncus arteriosus, sonologists should carefully search for the origin of the main pulmonary artery and for its 2 branches. Our experience suggests that wide‐band Doppler imaging facilitates the prenatal diagnosis of truncus arteriosus. © 2008 Wiley Periodicals, Inc. J Clin Ultrasound, 2009
The pheromonal gland of Lymantria dispar: Morphology and evidence for its innervation
Authors: Boi Marianna , Quartu Marina , Serra Maria Pina , Solari Paolo , Melis Tiziana , Del Fiacco Marina
Published: December 2008

The morphological features of the glandular epithelium that secretes pheromone in the polyphagous pest gypsy moth Lymantria dispar are described by light and electron microscopy. The monolayered gland cells are covered by the folded cuticle of the intersegmental membrane between the 8th and 9th abdominal segments showing neither sites of discontinuity nor distinct openings on its external surface. The cells bear a large, often irregularly shaped nucleus, and contain granules of variable amount and electron‐density. These granules are mostly located in the basal compartment of the cytoplasm, in a labyrinthine zone laying on a basement membrane. The apical membrane of the gland cells bear microvilli and cell–cell contact is established by different junctional structures. Nerve fibers enwrapped in glia are found beneath the basement membrane, in close contact with the secretory cells. This latter finding represents the first evidence of the innervation of the pheromonal gland in L. dispar. J. Morphol. 2009. © 2008 Wiley‐Liss, Inc.
Ultrastructure of the body cavities in Phylactolaemata (Bryozoa)
Authors: Gruhl Alexander , Wegener Ines , Bartolomaeus Thomas
Published: December 2008

Only species belonging to the bryozoan subtaxon Phylactolaemata possess an epistome. To test whether there is a specific coelomic cavity inside the epistome, Fredericella sultana, Plumatella emarginata, and Lophopus crystallinus were studied on the ultrastructural level. In F. sultana and P. emarginata, the epistome contains a coelomic cavity. The cavity is confluent with the trunk coelom and lined by peritoneal and myoepithelial cells. The lophophore coelom extends into the tentacles and is connected to the trunk coelom by two weakly ciliated coelomic ducts on either side of the rectum. The lophophore coelom passes the epistome coelom on its anterior side. This region has traditionally been called the forked canal and hypothesized to represent the site of excretion. L. crystallinus lacks an epistome. It has a simple ciliated field where an epistome is situated in the other species. Underneath this field, the forked canal is situated. Compared with the other species, it is pronounced and exhibits a dense ciliation. Despite the occurrence of podocytes, which are prerequisites for a selected fluid transfer, there is no indication for an excretory function of the forked canal, especially as no excretory porus was found. J. Morphol. 2009. © 2008 Wiley‐Liss, Inc.
Anatomy and ultrastructure of the female reproductive system of Pleioplana atomata (Platyhelminthes: Polycladida)
Authors: Liana Marcin K. , Litvaitis Marian K.
Published: December 2008

The ultrastructure of the female reproductive system of the polyclad flatworm Pleioplana atomata is described. Numerous ovaries are scattered throughout the entire body but are mainly concentrated on the dorsal side. Within an ovary, a germinative zone with oogonia and prefolicular cells is located in the dorsal part of the ovary. The remaining part of the gonad is filled with previtellogenic and early vitellogenic oocytes enwrapped by follicular cells. During previtellogenesis, oocytes produce numerous eggshell globules, which are distributed into the cortical area of the cell in later stages. Eventually, these globules release their contents into the space between the eggshell cover and oolemma. Similar types of globules are also found in others flatworms, and may represent useful phylogenetic characters. Entolecital, vitellogenic oocytes pass to paired uteri, where vitellogenesis is completed. The remainder of the female reproductive system consists of paired thin uterine ducts that join a vagina. The distal part of the long, curved vagina forms a large Lang's vesicle, while the proximal part is connected to a female atrium leading to a female gonopore. We hypothesize that Lang's vesicle functions in the digestion of excess sperm received. Two kinds of different shell (cement) glands that release their secretion into the vagina are identified. Both are unicellular glands and each gland cell connects to the lumen of the vagina via an individual canal. Similar glands in other acotylean polyclads have been implicated in the formation of eggshell covers. J. Morphol. 2009. © 2008 Wiley‐Liss, Inc.
Evolutionary morphology of the Tenrecoidea (Mammalia) hindlimb skeleton
Authors: Salton Justine A. , Sargis Eric J.
Published: December 2008

The tenrecs of Central Africa and Madagascar provide an excellent model for exploring adaptive radiation and functional aspects of mammalian hindlimb form. The pelvic girdle, femur, and crus of 13 tenrecoid species, and four species from the families Solenodontidae, Macroscelididae, and Erinaceidae, were examined and measured. Results from qualitative and quantitative analyses demonstrate remarkable diversity in several aspects of knee and hip joint skeletal form that are supportive of function‐based hypotheses, and consistent with studies on nontenrecoid eutherian postcranial adaptation. Locomotor specialists within Tenrecoidea exhibit suites of characteristics that are widespread among eutherians with similar locomotor behaviors. Furthermore, several characters that are constrained at the subfamily level were identified. Such characters are more indicative of postural behavior than locomotor behavior. J. Morphol., 2009. © 2008 Wiley‐Liss, Inc.
Three‐dimensional reconstruction of the odontophoral cartilages of Caenogastropoda (Mollusca: Gastropoda) using micro‐CT: Morphology and phylogenetic significance
Authors: Golding Rosemary E. , Ponder Winston F. , Byrne Maria
Published: December 2008

Odontophoral cartilages are located in the molluscan buccal mass and support the movement of the radula during feeding. The structural diversity of odontophoral cartilages is currently known only from limited taxa, but this information is important for interpreting phylogeny and for understanding the biomechanical operation of the buccal mass. Caenogastropods exhibit a wide variety of feeding strategies, but there is little comparative information on cartilage morphology within this group. The morphology of caenogastropod odontophoral cartilages is currently known only from dissection and histology, although preliminary results suggest that they may be structurally diverse. A comparative morphological survey of 18 caenogastropods and three noncaenogastropods has been conducted, sampling most major caenogastropod superfamilies. Three‐dimensional models of the odontophoral cartilages were generated using X‐ray microscopy (micro‐CT) and reconstruction by image segmentation. Considerable morphological diversity of the odontophoral cartilages was found within Caenogastropoda, including the presence of thin cartilaginous appendages, asymmetrically overlapping cartilages, and reflexed cartilage margins. Many basal caenogastropod taxa possess previously unidentified cartilaginous support structures below the radula (subradular cartilages), which may be homologous to the dorsal cartilages of other gastropods. As subradular cartilages were absent in carnivorous caenogastropods, adaptation to trophic specialization is likely. However, incongruence with specific feeding strategies or body size suggests that the morphology of odontophoral cartilages is constrained by phylogeny, representing a new source of morphological characters to improve the phylogenetic resolution of this group. J. Morphol. 2009. © 2008 Wiley‐Liss, Inc.