bluuebunny/crossref_metadata_2025_split huggingface dataset:
MMP‐2 sensitive, VEGF‐bearing bioactive hydrogels for promotion of vascular healing
Authors: Seliktar D. , Zisch A. H. , Lutolf M. P. , Wrana J. L. , Hubbell J. A. 
Published: February 2004

AbstractWe sought to develop bioactive hydrogels to facilitate arterial healing, e.g., after balloon angioplasty. Toward this end, we developed a new class of proteolytically sensitive, biologically active polyethylene glycol (PEG)‐peptide hydrogels that can be formed in situ to temporarily protect the arterial injury from blood contact. Furthermore, we incorporated endothelial cell‐specific biological signals with the goal of enhancing arterial reendothelialization. Here we demonstrate efficient endothelial cell anchorage and activation on PEG hydrogel matrices modified by conjugation with both the cell adhesive peptide motif RGD and an engineered variant of vascular endothelial growth factor (VEGF). By crosslinking peptide sequences for cleavage by MMP‐2 into the polymer backbone, the hydrogels became sensitive to proteolytic degradation by cell‐derived matrix metalloproteinases (MMPs). Analysis of molecular hallmarks associated with endothelial cell activation by VEGF‐RGD hydrogel matrices revealed a 70% increase in production of the latent MMP‐2 zymogen compared with PEG‐peptide hydrogels lacking VEGF. By additional provision of transforming growth factor β1 (TGF‐β1) within the PEG‐peptide hydrogel, conversion of the latent MMP zymogen into its active form was demonstrated. As a result of MMP‐2 activation, strongly enhanced hydrogel degradation by activated endothelial cells was observed. Our data illustrate the critical importance of growth factor activities for remodeling of synthetic biomaterials into native tissue, as it is desired in many applications of regenerative medicine. Functionalized PEG‐peptide hydrogels could help restore the native vessel wall and improve the performance of angioplasty procedures. © 2004 Wiley Periodicals, Inc. J Biomed Mater Res 68A: 704–716, 2004
In vitro biocorrosion of Ti‐6Al‐4V implant alloy by a mouse macrophage cell line
Authors: Lin Hsin‐Yi , Bumgardner Joel D. 
Published: February 2004

AbstractCorrosion of implant alloys releasing metal ions has the potential to cause adverse tissue reactions and implant failure. We hypothesized that macrophage cells and their released reactive chemical species (RCS) affect the alloy's corrosion properties. A custom cell culture corrosion box was used to evaluate how cell culture medium, macrophage cells and RCS altered the Ti‐6Al‐4V corrosion behaviors in 72 h and how corrosion products affected the cells. There was no difference in the charge transfer in the presence (75.2 ± 17.7 mC) and absence (62.3 ± 18.8 mC) of cells. The alloy had the lowest charge transfer (28.2 ± 4.1 mC) and metal ion release (Ti < 10 ppb, V < 2 ppb) with activated cells (releasing RCS) compared with the other two conditions. This was attributed to an enhancement of the surface oxides by RCS. Metal ion release was very low (Ti < 20 ppb, V < 10 ppb) with nonactivated cells and did not change cell morphology, viability, and NO and ATP release compared with controls. However, IL‐1β released from the activated cells and the proliferation of nonactivated cells were greater on the alloy than the controls. In summary, macrophage cells and RCS reduced the corrosion of Ti‐6Al‐4V alloys as hypothesized. These data are important in understanding host tissue‐material interactions. © 2004 Wiley Periodicals, Inc. J Biomed Mater Res 68A: 717–724, 2004
Fast‐setting calcium phosphate scaffolds with tailored macropore formation rates for bone regeneration
Authors: Xu Hockin H. K. , Takagi Shozo , Quinn Janet B. , Chow Laurence C. 
Published: February 2004

AbstractCalcium phosphate cement (CPC) is highly promising for craniofacial and orthopedic repair because of its ability to self‐harden in situ to form hydroxyapatite with excellent osteoconductivity. However, its low strength, long hardening time, and lack of macroporosity limit its use. This study aimed to develop fast‐setting and antiwashout CPC scaffolds with high strength and tailored macropore formation rates. Chitosan, sodium phosphate, and hydroxypropyl methylcellulose (HPMC) were used to render CPC fast‐setting and resistant to washout. Absorbable fibers and mannitol porogen were incorporated into CPC for strength and macropores for bone ingrowth. Flexural strength, work‐of‐fracture, and elastic modulus were measured vs. immersion time in a physiological solution. Hardening time (mean ± SD; n = 6) was 69.5 ± 2.1 min for CPC‐control, 9.3 ± 2.8 min for CPC‐HPMC‐mannitol, 8.2 ± 1.5 min for CPC‐chitosan‐mannitol, and 6.7 ± 1.6 min for CPC‐chitosan‐mannitol‐fiber. The latter three compositions were resistant to washout, whereas the CPC‐control paste showed washout in a physiological solution. Immersion for 1 day dissolved mannitol and created macropores in CPC. CPC‐chitosan‐mannitol‐fiber scaffold had a strength of 4.6 ± 1.4 MPa, significantly higher than 1.2 ± 0.1 MPa of CPC‐chitosan‐mannitol scaffold and 0.3 ± 0.2 MPa of CPC‐HPMC‐mannitol scaffold (Tukey's). The strength of CPC‐chitosan‐mannitol‐fiber scaffold was maintained up to 42 days and then decreased because of fiber degradation. Work‐of‐fracture and elastic modulus showed similar trends. Long cylindrical macropore channels were formed in CPC after fiber dissolution. The resorbable, fast‐setting, anti‐washout and strong CPC scaffold should be useful in craniofacial and orthopedic repairs. The novel method of combining fast‐ and slow‐dissolution porogens/fibers to produce scaffolds with high strength and tailored macropore formation rates to match bone healing rates may have wide applicability to other biomaterials. © 2004 Wiley Periodicals, Inc. J Biomed Mater Res 68A: 725–734, 2004
Crosslinking of collagen gels by transglutaminase
Authors: Orban Janine M. , Wilson Lorri B. , Kofroth Jessica A. , El‐Kurdi Mohammed S. , Maul Timothy M. , Vorp David A. 
Published: February 2004

AbstractCollagen is commonly used as a tissue‐engineering scaffold, yet its in vivo applications are limited by a deficiency in mechanical strength. The purpose of this work was to explore the utilization of a unique enzymatic crosslinking procedure aimed at improving the mechanical properties of collagen‐based scaffold materials. Type I bovine collagen gel was crosslinked by transglutaminase, which selectively mediates the chemical reaction between glutamine and lysine residues on adjacent protein fibers, thus providing covalent amide bonds that serve to reinforce the three‐dimensional matrix. The degree of crosslinking was verified by thermal analysis and amine group content. The denaturation temperature of crosslinked collagen reached a maximum of 66 ± 1°C. The chemical reaction was confirmed to be noncytotoxic with respect to bone marrow stromal cells acquired from New Zealand White rabbits. Tube‐shaped cellular constructs fashioned from crosslinked collagen and bone marrow stromal cells were found to have burst pressures significantly higher than their noncrosslinked analogs (71 ± 4 mmHg vs. 46 ± 3 mmHg; p < 0.01). Thus, the transglutaminase mediated reaction served to successfully strengthen collagen gels while remaining benign toward cells. © 2004 Wiley Periodicals, Inc. J Biomed Mater Res 68A: 756–762, 2004
Effect of chemical structure and composition of the resin phase on mechanical strength and vinyl conversion of amorphous calcium phosphate‐based composites
Authors: Skrtic D. , Antonucci J.M. , McDonough W.G. , Liu D.W. 
Published: February 2004

AbstractThe mechanical properties of recently developed bioactive, antidemineralizing/remineralizing, amorphous calcium phosphate (ACP)‐based composites need improvement. The objective of this study was to elucidate the effect of structure and composition of resins on the biaxial flexure strength (BFS) and the degree of conversion (DC) of composites attained after photo‐polymerization. Two series of 2,2‐bis[p‐(2′‐hydroxy‐3′‐methacryloxypropoxy)phenyl]propane (Bis‐GMA)/triethylene glycol dimethacrylate (TEGDMA)/X (X being a neutral or acidic comonomer) ternary resins were prepared and mixed with a mass fraction of 40% of zirconia‐hybridized ACP. Both unfilled copolymers and their composites were evaluated for BFS (dry and wet specimens after 2 weeks of immersion in buffered saline) and for DC (after 24 h at 23°C). It was found that for the neutral X monomers, no correlation existed between the hydrophobic/hydrophilic character of the X monomer and the BFS values of the immersed composites. A flexible monomethacrylate yielded copolymers and composites with the highest DC. For the resins utilizing the acidic comonomers, methacrylic acid and mono‐4‐(methacryloyloxy) ethyltrimellitate (4MET), dry composites with improved BFS values were obtained. 4MET composites exhibited the least loss of strength of all the ternary resin ACP materials. The effect of acidic X on DC was most pronounced for maleic acid copolymers. © 2004 Wiley Periodicals, Inc. J Biomed Mater Res 68A: 763–772, 2004
In vitro osteogenic differentiation of human mesenchymal stem cells photoencapsulated in PEG hydrogels
Authors: Nuttelman Charles R. , Tripodi Margaret C. , Anseth Kristi S. 
Published: February 2004

AbstractMuch research has focused on the differentiation of human mesenchymal stem cells (hMSCs) in monolayer culture; however, little is known about their differentiation potential in three‐dimensional culture conditions. In this research, hMSCs were encapsulated in a photocrosslinkable, injectable scaffolding system based on poly(ethylene glycol) (PEG) hydrogels. To demonstrate the ability of hMSCs to differentiate in PEG hydrogels, cell/polymer constructs were cultured in osteogenic differentiation media to elicit an osteoblastic response. First, viability of encapsulated hMSCs up to 4 weeks in culture was investigated using a membrane integrity assay. Second, gene expression of encapsulated cells was determined with reverse transcription polymerase chain reaction (RT‐PCR) as a function of media composition. After 1 week in osteogenic differentiation media, encapsulated hMSCs expressed osteonectin, osteopontin, and alkaline phosphatase, which are all characteristic of osteoblasts. Finally, von Kossa staining was used to evaluate mineralization of the PEG gels. Results support the hypothesis that hMSCs photoencapsulated in PEG hydrogels and cultured in the presence of osteogenic differentiation media are able to differentiate to osteoblasts inside the gel and mineralize the matrix. These experiments demonstrate the feasibility of using a PEG‐based, photocrosslinkable system to culture and deliver human mesenchymal stem cells for bone tissue regeneration and repair. © 2004 Wiley Periodicals, Inc. J Biomed Mater Res 68A: 773–782, 2004
Endotoxin increases hepatic susceptibility to lipid peroxidation: A possible role of iron
Authors: Ibrahim W. , Lee U.‐S. , Chow C. K. 
Published: February 2004

AbstractThe purpose of this study was to investigate the possible mechanism by which endotoxin enhances peroxidative damage to membrane lipids. Male B6C3 mice were treated with endotoxin intraperitoneally 0 or 20 mg/kg body weight for 24 h. Freshly prepared liver homogenate was incubated with either 1–5 mM of reduced glutathione (GSH), glucose, H2O2, ascorbic acid (AA), FeSO4, FeCl3, EDTA, FeCl3 plus AA, AA plus EDTA or EDTA plus FeCl3 in phosphate‐buffered saline (PBS), pH 7.0, or PBS, at 37°C for 60 min. The levels of lipid peroxidation products, thiobarbituric acid reactants (TBAR), were significantly higher in the liver of endotoxin‐treated mice, and the values were markedly increased following incubation. Compared to PBS, incubation with H2O2, FeCl3, FeSO4, and AA, but not glucose, significantly enhanced TBAR formation. The greatest increase of TBAR was found when AA and FeCl3 were added together. On the other hand, EDTA and GSH inhibited the formation of TBAR during incubation. When added before AA, EDTA completely inhibited the peroxidative effect of AA or FeSO4, and when added subsequent to AA, EDTA partially prevented the adverse effect of AA. The results obtained suggest that ionic iron plays an important role in initiating endotoxin‐induced peroxidative damage to membrane lipids, and that AA may be involved in releasing iron from its protein complex and/or maintaining ionic iron in a reduced or catalytic state. © 2004 Wiley Periodicals, Inc. J Biochem Mol Toxicol 18:23–29, 2004; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/jbt.20002
BMP7/ActRIIB regulates estrogen‐dependent apoptosis: New biomarkers for environmental estrogens
Authors: Kusumegi Takahiro , Tanaka Junko , Kawano Michihiro , Yonemoto Junzo , Tohyama Chiharu , Sone Hideko 
Published: February 2004

AbstractA ligand‐receptor pair, bone morphogenetic protein‐7 (BMP7) and activin receptor IIB (actRIIB), was identified from a pool of DNA fragments recovered from MCF7 cells treated with 17β‐estradiol (E2) by chromatin immunoprecipitation with antiestrogen receptor‐αantibody. The E2 responsiveness of both genes was confirmed in MCF cells and in the mouse uterus. Repeated treatment with E2 resulted in decreased expression of both actRIIB and BMP7 mRNA in the uteri of ovariectomized mice. A single oral administration of bisphenol A (BPA), an environmental estrogen, inhibited actRIIB and BMP7 expression and apoptosis in the luminal epithelium of the mouse uterus at diestrus (or early proestrus). This decrease, due to BPA administration, was restored by an estrogen receptor (ER) antagonist suggesting that it is mediated through ERs. These results suggest that E2 and BPA suppress estrogen‐dependent apoptosis of epithelial cells of the endometrium through down‐regulation of actRIIB and BMP7. Thus, we propose that BMP7 and actRIIB, a ligand‐receptor pair, are involved in regulation of the apoptotic signaling pathway and might therefore be new biomarkers of the effects of environmental estrogens on the female reproductive tract. © 2004 Wiley Periodicals, Inc. J Biochem Mol Toxicol 18:1–11, 2004; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/jbt.20004
New insights into the mechanisms involved in renal proximal tubular damage induced in vitro by ochratoxin A
Authors: Gennari Alessandra , Pazos Patricia , Boveri Monica , Callaghan Robert , Casado Juan , Maurici Daniela , Corsini Emanuela , Prieto Pilar 
Published: February 2004

AbstractThe mycotoxin ochratoxin A is a contaminant of human and animal food products. It is a potent nephrotoxin known to damage the proximal tubule. The aim of this work was to investigate the effects of ochratoxin A on a porcine renal proximal tubular epithelial cell line (LLC‐PK1), and to identify sensitive endpoints revealing damage at the epithelial barrier level and at the molecular level. Cells exposed for 24 h to 5–10 μM ochratoxin indicated a clear damage to the intactness of the epithelial barrier, as shown by measurements of trans‐epithelial resistance and zonula occludens‐1 protein expression. At the mitochondrial level we observed alterations of the normal functions, such as an increase of the membrane potential, the formation of straight extensions, and the formation of giant mitochondria. At higher ochratoxin concentrations (50 μM), at which cytotoxicity assays revealed a significant toxicity, alterations of the cytoskeleton organization and induction of apoptosis were evident. In addition, we analyzed the expression of genes by using a cDNA macroarray. Our data indicate that ochratoxin‐induced nephrotoxicity can be detected at the barrier and at the mitochondrial level at rather low concentrations, at which conventional cytotoxicity assays are unable to reveal toxic effects. © 2004 Wiley Periodicals, Inc. J Biochem Mol Toxicol 18:43–49, 2004; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/jbt.20006
Generation of an oxidative stress precedes caspase activation during 7β‐hydroxycholesterol‐induced apoptosis in U937 cells
Authors: Ryan Lisa , O'Callaghan Yvonne C. , O'Brien Nora M. 
Published: February 2004

AbstractThe oxysterol 7beta‐hydroxycholesterol (7β‐OH) has been shown to induce apoptosis in a number of cell lines. Though not fully elucidated, the mechanism through which this oxysterol induces cell death is thought to involve the generation of an oxidative stress leading to perturbation of the mitochondrion and release of cytochrome c into the cytosol. Cytochrome c together with Apaf‐1 causes activation of the initiator caspase, caspase‐9, which in turn activates caspase‐3 ultimately leading to the degradation of poly(ADP‐ribose) polymerase (PARP). The objective of the present study was to investigate the signalling pathway in 7β‐OH‐induced apoptosis in U937 cells, a human monocytic blood cell line known to undergo apoptosis upon treatment with 7β‐OH, over a time course of 48 h. Apoptosis was evident after 24 h incubation. Glutathione levels were decreased after 6 h and this was coupled with an increase in SOD activity. Through western blot analysis we examined expression of caspase‐3, ‐8, and ‐9 and cleavage of the caspase‐3 substrate PARP. The sequence proceeded with activation of caspase‐9 after 9 h, caspase‐3 at the 12 h timepoint, and cleavage of PARP after 24 h treatment with 7β‐OH. Caspase‐8 did not appear to play a major role in this particular apoptotic pathway. © 2004 Wiley Periodicals, Inc. J Biochem Mol Toxicol 18:50–59, 2004; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/jbt.20007
Need cash? Don't forget leveraged recaps
Authors: Hooke Jeff 
Published: February 2004

AbstractLeveraged recapitalizations are viable alternatives for entrepreneurial firms and family businesses that are
shut off from reasonable pricing in the IPO and M&A markets. Recaps are also useful tools for large
corporations—especially when they need cash from a division but want to retain a portion of the
division's operating upside. © 2004 Wiley Periodicals, Inc.
Using ABC to manage and improve at CONCO foods
Authors: Schulist Stephen 
Published: February 2004

AbstractActivity‐based costing (ABC) is a journey not a destination. It has evolved from its beginnings
into an ongoing process that is more aptly called profitability management. Profitability
management is the process of using information from an ABC software tool to continually manage and improve the
business. © 2004 Wiley Periodicals, Inc.
Prostate cancer bone metastases promote both osteolytic and osteoblastic activity
Authors: Keller Evan T. , Brown Julie 
Published: February 2004

AbstractAdvanced prostate cancer is frequently accompanied by the development of metastasis to bone. In the past, prostate cancer bone metastases were characterized as being osteoblastic (i.e., increasing bone density) based on radiographs. However, emerging evidence suggests that development of prostate cancer bone metastases requires osteoclastic activity in addition to osteoblastic activity. The complexities of how prostate tumor cells influence bone remodeling are just beginning to be elucidated. Prostate cancer cells produce a variety of pro‐osteoblastic factors that promote bone mineralization. For example, both bone morphogenetic proteins and endothelin‐1 have well recognized pro‐osteoblastic activities and are produced by prostate cancer cells. In addition to factors that enhance bone mineralization prostate cancer cells produced factors that promote osteoclast activity. Perhaps the most critical pro‐osteoclastogenic factor produced by prostate cancer cells is receptor activator of NFκB ligand (RANKL), which has been shown to be required for the development of osteoclasts. Blocking RANKL results in inhibiting prostate cancer‐induced osteoclastogenesis and inhibits development and progression of prostate tumor growth in bone. These findings suggest that targeting osteoclast activity may be of therapeutic benefit. However, it remains to be defined how prostate cancer cells synchronize the combination of osteoclastic and osteoblastic activity. We propose that as the bone microenvironment is changed by the developing cancer, this in turn influences the prostate cancer cells' balance between pro‐osteoclastic and pro‐osteoblastic activity. Accordingly, the determination of how the prostate cancer cells and bone microenvironment crosstalk are important to elucidate how prostate cancer cells modulate bone remodeling. © 2003 Wiley‐Liss, Inc.
Modulation of prostate cancer growth in bone microenvironments
Authors: Edlund Magnus , Sung Shian‐Ying , Chung Leland W.K. 
Published: February 2004

AbstractBone remains one of the major sites, and most lethal host organs, for prostate cancer metastasis. Prostate cell spread and establishment in bone depends on multiple reciprocal modifications of bone stromal and epithelial cancer cell behaviors. This review focuses on recent advances in the characterization of cell–cell and cell–matrix interplay, effects on cell growth, adhesion and invasion, and several therapeutic possibilities for co‐targeting prostate cancer cells and bone stroma. We address the topic from three main perspectives: (1) the normal and aging bone stromal environment, (2) the “reactive” bone stromal environment, and (3) the cancerous prostate epithelial cells themselves. First, normal, and especially aging, bones provide uniquely rich and “fertile soil” for roaming cancer cells. The interactions between prostate cancer cells and insoluble extracellular matrices, soluble growth factors, and/or sex steroid hormones trigger bone remodeling, through increased osteoclastogenesis and furthur matrix metalloproteinase activity. Second, after cancer cell arrival and establishment in the bone, host stromal cells respond, becoming “reactive” in a process again involving extracellular matrix remodeling, together with growth factor and steroid receptor signaling this process ultimately enhances cancer cell migration, stromal transdifferentiation, and invasion of the cancer tissues by stromal, inflammatory, and immune‐responsive cells. Third, prostate cancer cells also respond to supportive bone microenvironments, where soluble and matrix‐associated molecules affect cancer cell growth and gene expression, especially altering cancer cell surface receptor and integrin‐mediated cell signaling. We discuss both integrin cell–matrix and gap junctional cell–cell communication between cancer cells and their microenvironments during prostate cancer progression. © 2003 Wiley‐Liss, Inc.
Immunolocalization of detergent‐susceptible nucleoplasmic lamin A/C foci by a novel monoclonal antibody
Authors: Muralikrishna Bh. , Thanumalayan S. , Jagatheesan G. , Rangaraj Nandini , Karande Anjali A. , Parnaik Veena K. 
Published: February 2004

AbstractThe A‐type lamins are localized in the interior of the nucleus as well as on the nuclear periphery. In this study, we have characterized a monoclonal antibody LA‐2F9 produced against recombinant rat lamin A which stains a subpopulation of various cell types in a pattern of small nucleoplasmic foci that are unusually susceptible to mild detergent/salt extraction. The specific reactivity of mAb LA‐2F9 towards lamins was confirmed by immunoblotting of HeLa and C3H10T½ whole cell lysates and nuclear lysates. The epitope for LA‐2F9 was narrowed down to amino acid residues 268–278 (SAKLDNARQSA). To check whether the appearance of lamin foci was cell‐cycle‐dependent, C3H10T½ cells were serum‐starved and then refed to trigger cells to enter the G1 phase of the cell‐cycle. The intensity of staining increased 3.5‐fold within 6 h of refeeding, when the maximum number of cells were labeled with LA‐2F9. We also checked whether the LA‐2F9 foci colocalized with nuclear proteins known to be distributed in small foci such as hnRNPs, snRNPs, SC‐35, and p80 coilin, but did not find evidence of colocalization. Our studies suggest that LA‐2F9 has a novel and specific reactivity towards detergent‐susceptible lower order lamin structures that are likely to be assembly intermediates. © 2004 Wiley‐Liss, Inc.