bluuebunny/crossref_metadata_2025_split huggingface dataset:
Relative risk of prostate cancer for men with affected relatives: Systematic review and meta‐analysis
Authors: Watkins Bruner Deborah , Moore Dirk , Parlanti Alicia , Dorgan Joanne , Engstrom Paul 
Published: October 2003

AbstractAn increased risk of prostate cancer associated with a family history of prostate cancer has been documented in multiple published reports. Risk has been shown to vary by degree of relationship and age of onset of disease in the affected relative. Several studies, using various designs, have estimated the relative risk (RR) for these associations. The purpose of our study was to identify and summarize published reports on the relationship between risk of prostate cancer and family history, which is defined as having a father, brother, any first‐ or second‐degree relative or other relative affected with prostate cancer. A Medline and manual search from 1982 to 2000 identified 24 studies that reported RR and confidence intervals (CI) and satisfied inclusion criteria. Pooled RR estimates based upon a weighted average model were as follows: any affected family member RR = 1.93, CI 1.65–2.26; affected first‐degree relative RR = 2.22, CI 2.06–2.40; affected second‐degree relative RR = 1.88, CI 1.54–2.30; father with prostate cancer RR = 2.12, CI 1.82–2.51; and brother with prostate cancer RR = 2.87, CI 2.21–3.73). Statistical comparison of pooled data demonstrated that the RR is significantly higher for affected brother than for affected father (p < 0.03). A sensitivity analysis demonstrated that these results are robust with respect to population bias. This meta‐analysis confirms that risk of prostate cancer is associated with family history of disease and improves the quantification of this risk. © 2003 Wiley‐Liss, Inc.
Condom use promotes regression of cervical intraepithelial neoplasia and clearance of human papillomavirus: A randomized clinical trial
Authors: Hogewoning Cornelis J.A. , Bleeker Maaike C.G. , van den Brule Adriaan J.C. , Voorhorst Feja J. , Snijders Peter J.F. , Berkhof Johannes , Westenend Pieter J. , Meijer Chris J.L.M. 
Published: October 2003

AbstractWomen with persistent HPV infections have increased risk of progressive CIN lesions. Transmission of HPV between sexual partners might maintain viral infection and, consequently, may influence the clinical course of CIN. We investigated the effect of condom use on regression of CIN lesions and on clearance of HPV. Women with CIN and their male sexual partners were randomized for condom use (condom group n = 72 and noncondom group n = 76). They were conservatively managed and followed every 3–6 months by colposcopy, cytology and HPV testing by GP5+/6+ PCR. Baseline cervical biopsy specimens were taken. Median follow‐up time for women was 15.2 months (range 3.0–85.4). Outcomes of interest were clinical regression of CIN at colposcopy and clearance of HPV. Outcomes were assessed in 64 women of the condom group and 61 women of the noncondom group. Women in the condom group showed a 2‐year cumulative regression rate of 53% vs. 35% in the noncondom group (p = 0.03). The 2‐year cumulative rates of HPV clearance were 23% vs. 4%, respectively (p = 0.02). Although lower regression rates were found if women were HPV‐positive and had ≥CIN2 lesions at baseline, effects of condom use were found both in women with CIN1 and in women with ≥CIN2 lesions. Condom use promotes regression of CIN lesions and clearance of HPV. © 2003 Wiley‐Liss, Inc.
HER‐2 and TOP2A coamplification in urinary bladder cancer
Authors: Simon Ronald , Atefy Ramin , Wagner Urs , Forster Thomas , Fijan André , Bruderer James , Wilber Kim , Mihatsch Michael J. , Gasser Thomas , Sauter Guido 
Published: October 2003

AbstractHER‐2/NEU is one of the most frequently amplified oncogenes and a potential therapeutic target in bladder cancer. In breast cancer, the adjacent TOP2A gene, the molecular target for several anticancer drugs, is frequently coamplified together with HER‐2. To study the amplification and expression of TOP2A and HER‐2 and associations with tumor phenotype and clinical outcome in bladder cancer, a tissue microarray containing 2,317 bladder tumor samples was analyzed by FISH and immunohistochemistry. Overall amplification frequencies were 6.3% for HER‐2 and 1.5% for TOP2A. Amplifications were most frequently seen in advanced‐stage (pT2–4) tumors (HER‐2 13.8%, TOP2A 3.4%). Of HER‐2‐amplified tumors, 56% also had alterations of TOP2A, including 14.7% coamplifications, 33.3% gains and 8% deletions. Only 17.6% of TOP2A amplifications occurred independently of HER‐2 alterations. Both HER‐2 and TOP2A amplifications were significantly associated with advanced tumor stage (HER‐2
p < 0.0001, TOP2A
p = 0.0218), high grade (p < 0.0001 for both) and protein overexpression (p < 0.0001 for both). TOP2A amplification and overexpression were linked to shortened survival in muscle‐invasive tumors (p = 0.0042 and 0.0077, respectively). In summary, our data suggest that HER‐2 amplifications are frequently linked to alterations of the TOP2A gene in bladder cancer. The anatomy of the 17q12‐q21 amplicon may be important for response to therapies targeting HER‐2 or TOP2A. © 2003 Wiley‐Liss, Inc.
Identification of a sperm protein 17 CTL epitope restricted by HLA‐A1
Authors: Chiriva‐Internati Maurizio , Wang Zhiqing , Pochopien Stephanie , Salati Emanuela , Lim Seah H. 
Published: October 2003

AbstractSperm protein 17 (Sp17) is a novel cancer‐testis antigen. We previously reported the successful generation of Sp17‐specific HLA‐A1‐restricted cytotoxic T‐lymphocytes (CTLs) from the peripheral blood of a healthy donor using a recombinant Sp17 protein. These CTLs were able to kill not only target cells pulsed with the recombinant protein but also fresh Sp17+ tumor cells. In the present study, we have identified a nonapeptide sequence within the Sp17 protein that is predicted to have a high binding affinity for the HLA‐A1 molecules. We generated the synthetic nonapeptide and successfully propagated a peptide‐specific CTL line. We confirmed that peptide Sp17103–111 (ILDSSEEDK) contains an Sp17 CTL epitope restricted by HLA‐A1 and identified amino acid residues 104, 107, 109 and 110 as crucial for the CTL lysis. Our findings therefore provide the tool for the characterization of CD8 T‐cell function in vivo and generation of epitope‐specific treatment strategies. © 2003 Wiley‐Liss, Inc.
A biodegradable polyurethane‐ascorbic acid scaffold for bone tissue engineering
Authors: Zhang Jianying , Doll Bruce A. , Beckman Eric J. , Hollinger Jeffrey O. 
Published: October 2003

AbstractA novel, nontoxic, biodegradable, sponge‐like polyurethane scaffold was synthesized from lysine‐di‐isocyanate (LDI) and glycerol. Ascorbic acid (AA) was copolymerized with LDI‐glycerol. Our hypothesis was that the AA‐containing polymer foam would enhance the biological activity of the osteoblastic precursor cell (OPCs). The LDI‐glycerol‐AA matrix degraded in aqueous solution to the nontoxic products of lysine, glycerol, and AA. The degradation products did not significantly affect the solution pH. The physical properties of the polymer network supported the cell growth in vitro. Mouse OPCs attached to the polymer matrix and remained viable. OPCs produced multilayered confluent cultures, a characteristic typical of bone cells. Furthermore, AA release stimulated cell proliferation, type I collagen, and alkaline phosphatase synthesis. Cells grown on the LDI‐glycerol‐AA matrix also showed an enhancement of mRNA expression for pro‐α1 (I) collagen and transforming growth factor‐α1 after 1 week. Data were tested for significance with an analysis of variance model and multiple comparison test (Fisher's Protected Least Significant Difference) at p ≤ 0.05. The observations suggest that AA‐containing polyurethane may be useful in bone tissue engineering applications. © 2003 Wiley Periodicals, Inc. J Biomed Mater Res 67A: 389–400, 2003
Effective removal of alginate‐poly‐L‐lysine microcapsules from pancreatic islets by use of trypsin–EDTA
Authors: de Groot Martijn , Leuvenink Henri G. D. , Keizer Paula P. M. , Fekken Susan , Schuurs Theo A. , van Schilfgaarde Reinout 
Published: October 2003

AbstractAlthough the transplantation of alginate‐poly‐L‐lysine‐alginate encapsulated islets of Langerhans usually is successful, graft survival is still limited. Molecular analysis by RT‐PCR of the encapsulated islets may provide insight into the mechanisms that affect islets during graft failure. However, RT‐PCR on encapsulated islets is not possible because the poly‐L‐lysine of the capsule interferes with both cDNA synthesis and PCR amplification. We applied a method that mechanically removes the microcapsules from the islets after a short trypsin–EDTA treatment (decapsulation), thereby enabling RT‐PCR analysis. The results of this study show that the decapsulation procedure does not affect islet vitality and has only minor effects on islet function and morphology. The decapsulation does not affect GAPDH, β‐actin, Bcl‐2, or Bax gene expression. This method is an improvement over the time‐consuming manual dissection of microcapsules because it allows for the rapid and relatively harmless removal of capsules on a larger scale. Decapsulation offers the possibility of applying RT‐PCR, as well as other methods, which cannot be performed on encapsulated islets. © 2003 Wiley Periodicals, Inc. J Biomed Mater Res 67A: 679–683, 2003
Biologically inspired synthesis of bone‐like composite: Self‐assembled collagen fibers/hydroxyapatite nanocrystals
Authors: Tampieri Anna , Celotti Giancarlo , Landi Elena , Sandri Monica , Roveri Norberto , Falini Giuseppe 
Published: October 2003

AbstractReplacement of bone tissue by graft materials and products of tissue engineering having composition, structure, and biological features that mimic natural tissue is a goal to be pursued. A biomimetic synthesis was performed to prepare new bone‐like composites constituted of hydroxyapatite nanocrystals and self‐assembled type I collagen fibers. We used a biological inspired approach that proved that the biological systems stored and processed information at the molecular level. Two different methodologies were used: dispersion of synthetic hydroxyapatite in telopeptides free collagen molecules solution and direct nucleation of hydroxyapatite into reconstituted collagen fibers during their assembling. The different preparation techniques were experimented then the composites thoroughly characterized and compared. Composite obtained by direct nucleation showed an intimated interaction of the inorganic and proteic components, which modified the apatitic phase and made its composition, morphology and structure similar to the mineral component of natural bone. © 2003 Wiley Periodicals, Inc. J Biomed Mater Res 67A: 618–625, 2003
Synthesis of cytoadhesive poly(methylmethacrylate) for applications in targeted drug delivery
Authors: Tao Sarah L. , Lubeley Michael W. , Desai Tejal A. 
Published: October 2003

AbstractThe objective of this work was to incorporate cytoadhesive properties into poly(methylmethacrylate) (PMMA) for potential applications in highly localized tissue‐specific drug delivery. First, the PMMA was chemically modified by aminolysis to yield amine‐terminated surfaces. X‐ray photoelectron microscopy confirmed the presence of surface nitrogen entities, and the distribution of amine groups was found to be relatively uniform, as characterized by atomic force microscopy. The availability of these groups for attachment of biologically active molecules was characterized by fluorescence microscopy after immobilization of avidin‐FITC. To render the PMMA cytoadhesive, avidin molecules were conjugated to the amine‐terminated surfaces with a hydroxy‐succinimide‐catalyzed carbodiimide reagent and biotin‐labeled lectins (tomato, which binds selectively to Caco‐2 cells, and peanut, an unrelated lectin) subsequently were attached utilizing avidin‐biotin chemistry. Cytoadhesive activity was evaluated by characterizing the interactions between microfabricated PMMA particles and Caco‐2 monolayers. After 15‐, 30‐, 60‐, and 120‐min incubation periods, the tomato lectin‐conjugated PMMA showed a two to sixfold increase in Caco‐2 cell recognition over control particles. Furthermore, the stability of the cytoadhesive PMMA interactions appeared to be three to seven times greater than that of the control surfaces. These findings demonstrate the cytoadhesive properties of modified PMMA, making this novel bioactive polymer very promising for applications in targeted drug delivery. © 2003 Wiley Periodicals, Inc. J Biomed Mater Res 67A: 369–375, 2003
Development of a porous poly(L‐lactic acid)/hydroxyapatite/collagen scaffold as a BMP delivery system and its use in healing canine segmental bone defect
Authors: Hu Yunyu , Zhang Chao , Zhang Shuming , Xiong Zhuo , Xu Jianqiang 
Published: October 2003

AbstractA hydroxyapatite/collagen (HAC) composite was produced to mimic the natural extracellular matrix of bone, with the collagen serving as a template for apatite formation. A three‐dimensional highly porous scaffold was developed by mixing HAC with poly(L‐lactic acid) (PLA) using a thermally induced phase separation technique. Naturally derived bovine bone morphogenetic protein (bBMP) was incorporated into the porous HAC‐PLA scaffolds, and the composite then was implanted in diaphyseal defects (2 cm in radius) of adult beagle dogs. Controls were implanted with scaffolds without BMP. The dogs were sacrificed at 6 months, at which time biocompatibility, biodegradability, and osteoinduction were evaluated by histologic and radiologic examination and by bone mineral density (BMD) measurements. All defects healed after treatment with BMP combined with HAC‐PLA, and BMD at the site of the defect was higher than the BMD of the intact radius. Fibrous union developed in the control group animals. Histologic observation indicated that the presence of BMP not only promoted osteogenesis but that it also accelerated degradation of the biomaterials. Optimized design parameters of a three‐dimensional porous biomaterial would give full scope to the role of BMP as an osteoinductive growth factor. © 2003 Wiley Periodicals, Inc. J Biomed Mater Res 67A: 591–598, 2003
On the fracture of human dentin: Is it stress‐ or strain‐controlled?
Authors: Nalla R. K. , Kinney J. H. , Ritchie R. O. 
Published: October 2003

AbstractDespite substantial clinical interest in the fracture resistance of human dentin, there is little mechanistic information in archival literature that can be usefully used to model such fracture. In fact, although the fracture event in dentin, akin to other mineralized tissues like bone, is widely believed to be locally strain‐controlled, there has never been any scientific proof to support this belief. The present study seeks to address this issue through the use of a novel set of in vitro experiments in Hanks' balanced salt solution involving a double‐notched bend test geometry, which is designed to discern whether the critical failure events involved in the onset of fracture are locally stress‐ or strain‐controlled. Such experiments are further used to characterize the notion of “plasticity” in dentin and the interaction of cracks with the salient microstructural features. It is observed that fracture in dentin is indeed locally strain‐controlled and that the presence of dentinal tubules does not substantially affect this process of crack initiation and growth. The results presented are believed to be critical steps in the development of a micromechanical model for the fracture of human dentin that takes into consideration the influence of both the microstructure and the local failure mode. © 2003 Wiley Periodicals, Inc. J Biomed Mater Res 67A: 484–495, 2003
Oxygen radical production in neutrophils interacting with platelets and surface‐immobilized plasma proteins: Role of tyrosine phosphorylation
Authors: Nimeri Ghada , Majeed Meytham , Elwing Hans , Öhman Lena , Wetterö Jonas , Bengtsson Torbjörn 
Published: October 2003

AbstractThe interaction between neutrophil granulocytes and platelets is considered to play an important role in the inflammatory process induced by an implanted foreign material. However, the cellular mechanisms involved remain incompletely understood. We used a luminol‐dependent chemiluminescence (CL) technique to analyze the generation of reactive oxygen species (ROS) in human neutrophils interacting with different plasma protein‐coated surfaces in the presence or absence of unstimulated or stimulated platelets. The role of tyrosine phosphorylation in the regulation of NADPH oxidase activity was evaluated with quantitative fluorescence microscopy and the specific tyrosine kinase inhibitor genistein. We found that the ROS‐production is 2 to 3 times higher in neutrophils on immunoglobulin G (IgG)‐coated surfaces than in cells interacting with albumin‐ or fibrinogen‐coated surfaces. Incubation with superoxide dismutase and catalase revealed that about 45% of the ROS was released extracellularly on IgG surfaces whereas corresponding values were 90% and 85% in neutrophils interacting with albumin and fibrinogen, respectively. The presence of platelets markedly increased the extracellular generation of ROS, mainly in neutrophils interacting with IgG‐ or fibrinogen‐coated surfaces whereas the intracellular production was only modestly affected. Quantitative fluorescence microscopy of neutrophils stained with FITC‐conjugated anti‐phosphotyrosine antibodies showed a correlation between tyrosine phosphorylation, cell spreading, and ROS production. Platelets markedly amplified the anti‐phosphotyrosine staining on both fibrinogen‐ and IgG‐coated surfaces whereas the low level of tyrosine phosphorylation in neutrophils on albumin‐coated surfaces was not further elevated by platelets. Furthermore, the tyrosine kinase inhibitor genistein inhibited both extra‐ and intracellular ROS production in neutrophils regardless of the presence of platelets. We demonstrate that plasma protein coating and the presence of platelets are crucial for the inflammatory response of adhering neutrophils and that the oxidative response correlates with the extent of tyrosine phosphorylation of proteins in focal contacts. © 2003 Wiley Periodicals, Inc. J Biomed Mater Res 67A: 439–447, 2003
Biocompatibility of collagen membranes crosslinked with glutaraldehyde or diphenylphosphoryl azide: An in vitro study
Authors: Marinucci Lorella , Lilli Cinzia , Guerra Mario , Belcastro Salvatore , Becchetti Ennio , Stabellini Giordano , Calvi Edoardo M. , Locci Paola 
Published: October 2003

AbstractCrosslinking of collagen biomaterials increases their resistance to degradation in vivo. Glutaraldehyde (GA) is normally used to crosslink collagen biomaterial, but is often cytotoxic. Diphenylphosphoryl azide (DPPA) has recently been proposed as reagent, but little is known about its effects on cell behavior. In this study, we determined which collagen membrane was the most biocompatible: Paroguide which is crosslinked with DPPA and contains chondroitin sulfate; Opocrin which is crosslinked with DPPA; Biomed Extend which is crosslinked with GA; and Bio‐Gide which is left untreated. Cell proliferation and extracellular matrix macromolecule deposition were evaluated in human fibroblasts cultured on the membranes. The GA‐crosslinked Biomed Extend membrane and the not‐crosslinked Bio‐Gide membrane reduced cell growth and collagen secretion compared with DPPA‐crosslinked biomembranes. When Paroguide and Opocrin were compared, better results were obtained with Paroguide. The greatest amount of transforming growth factor β1, a growth factor involved in extracellular matrix macromolecule accumulation and in tissue regeneration, was produced by cells cultured on Paroguide, with Opocrin second. Our data suggest that the DPPA method is more biocompatible than the GA for crosslinking collagen biomaterials and that membranes made of collagen plus chondroitin sulfate are better than membranes made of pure collagen. © 2003 Wiley Periodicals, Inc. J Biomed Mater Res 67A: 504–509, 2003
Modification of Ti6AL4V surfaces using collagen I, III, and fibronectin. II. Influence on osteoblast responses
Authors: Bierbaum Susanne , Hempel Ute , Geißler Ulrike , Hanke Thomas , Scharnweber Dieter , Wenzel Klaus‐Wolfgang , Worch Hartmut 
Published: October 2003

AbstractResponses of osteoblastic cells are influenced by morphology and composition of the extracellular matrix, and this fact has been used to improve the biological acceptance of implants by modifying the surfaces with components of the extracellular matrix (ECM). In this study, the effect of the collagen types I and III on adhesion, proliferation, and differentiation was studied, using primary osteoblastic cells from rat calvariae. Differences in alkaline phosphatase activity (ALP) and collagen synthesis were observed between differently composed collagen coatings. An increase in collagen type III resulted in an increase in collagen synthesis and a concomitant decrease in ALP activity and Ca deposition. Initial adhesion mechanism of the cells depended on the substrate (titanium, collagen, fibronectin). © 2003 Wiley Periodicals, Inc. J Biomed Mater Res 67A: 431–438, 2003
Nano‐fibrous scaffolding architecture selectively enhances protein adsorption contributing to cell attachment
Authors: Woo Kyung Mi , Chen Victor J. , Ma Peter X. 
Published: October 2003

AbstractTissue engineering aims at resolving problems such as donor shortage and immune rejection faced by transplantation. Scaffolds (artificial extracellular matrices) have critical roles in tissue engineering. Recently, we developed nano‐fibrous poly(L‐lactic acid) scaffolds under the hypothesis that synthetic nano‐fibrous scaffolding, mimicking the structure of natural collagen fibers, could create a more favorable microenvironment for cells. This is the first report that the nano‐fibrous architecture built in three‐dimensional scaffolds improved the features of protein adsorption, which mediates cell interactions with scaffolds. Scaffolds with nano‐fibrous pore walls adsorbed four times more serum proteins than scaffolds with solid pore walls. More interestingly, the nano‐fibrous architecture selectively enhanced protein adsorption including fibronectin and vitronectin, even though both scaffolds were made from the same poly(L‐lactic acid) material. Furthermore, nano‐fibrous scaffolds also allowed >1.7 times of osteoblastic cell attachment than scaffolds with solid pore walls. These results demonstrate that the biomimetic nano‐fibrous architecture serves as superior scaffolding for tissue engineering. © 2003 Wiley Periodicals, Inc. J Biomed Mater Res 67A: 531–537, 2003
Optimal heparin surface concentration and antithrombin binding capacity as evaluated with human non‐anticoagulated blood in vitro
Authors: Andersson Jonas , Sanchez Javier , Ekdahl Kristina Nilsson , Elgue Graciela , Nilsson Bo , Larsson Rolf 
Published: October 2003

AbstractContact between blood and a biomaterial surface takes place in many applications and is known to activate the coagulation and complement systems. Heparin surface coatings have been shown to reduce blood activation upon contact with artificial surfaces. To establish the optimal heparin surface concentration, blood was incubated in a tubing loop model at 37°C. The tubing was coated with different surface concentrations of heparin and rotated at three different velocities. We demonstrate that the blood compatibility of a surface with regard to coagulation, complement, and platelet activation can be improved by increasing the heparin surface concentration in the 6–12 pmol antithrombin/cm2 concentration interval. The binding of factor H is not influenced by the increased heparin surface concentration, suggesting that this factor is not the primary regulator of complement on heparin surfaces. In addition, the heparin coating has no effect on the complement activation that occurs on gas surfaces in extracorporeal circuits. © 2003 Wiley Periodicals, Inc. J Biomed Mater Res 67A: 458–466, 2003