bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prefabrication of vascularized bone graft using a combination of fibroblast growth factor‐2 and vascular bundle implantation into a novel interconnected porous calcium hydroxyapatite ceramic
Authors: Nakasa Tomoyuki , Ishida Osamu , Sunagawa Toru , Nakamae Atsuo , Yasunaga Yuji , Agung Muhammad , Ochi Mitsuo 
Published: August 2005

AbstractThe aim of this study was to create a prefabricated vascularized bone graft using a novel interconnected porous calcium hydroxyapatite ceramic (IP‐CHA) by combining vascular bundle implantation and basic fibroblast growth factor (FGF)‐2 administration in a rabbit model. Twenty‐four Japanese white rabbits were used. The saphenous artery and vein were passed through the hole of the IP‐CHA. In an experimental group, 100 μg of FGF‐2 was administered into the IP‐CHA before implanting the vascular bundle. In the control group, the saline was administered into the IP‐CHA before implanting the vascular bundle. Finally, the IP‐CHA was placed subcutaneously in the medial thigh. Neovascularization from the vascular bundle was evaluated at 2 weeks after surgery, and osteogenesis was evaluated at 4 weeks. At 2 weeks, the length and density of newly formed vessels were significantly greater in the experimental group than in the control group. Histological evaluation showed osteoid deposition in the pores of the IP‐CHA at 4 weeks in the experimental group, whereas no evidence of osteoid deposition was noted in the control group. This study showed the potential of creating a vascularized bone graft of a predetermined size and shape using a combination of FGF‐2 and vascular bundle implantation in the IP‐CHA. © 2005 Wiley Periodicals, Inc. J Biomed Mater Res, 2005
In vitro induction of polyploidy and chromatid exchanges by culture medium extracts of natural rubbers compounded with 2‐mercaptobenzothiazole as a positive control candidate for genotoxicity tests
Authors: Matsuoka Atsuko , Isama Kazuo , Tsuchiya Toshie 
Published: August 2005

AbstractWe tested extracts of custom‐made natural rubber samples for cytotoxicity using V79 cells and for chromosome aberration (CA) induction using CHL cells in compliance with the Japanese guidelines for basic biological tests of medical materials and devices. The samples were formulated with a high level of 2‐mercaptobenzothiazole (MBT) (A); a low level of MBT (B); or zinc dibutyldithiocarbamate (ZDBC) (C). In the CA test, MBT induced mainly polyploidy, including endoreduplication, and ZDBC induced structural CAs. In the cytotoxicity test, culture medium extracts of A, B, and C suppressed colony formation to 50% of the control value at 53.1%, 94.3%, and >100%, respectively. Culture medium extracts of sample A induced polyploidy and structural CAs in the absence of an exogenous metabolic activation system (S9 mix), but at lower concentrations in its presence, indicating the existence of other leachable promutagens. The extracts of sample B induced structural CAs at the highest concentration and only with S9 mix. Sample C was negative. The facts suggest that sample A may be a candidate for a positive control for genotoxicity tests. The high frequency of polyploidy induced by sample A was not predicted by MBT, suggesting the usefulness of the test for safety evaluation of medical devices. Numerical CAs induced by MBT and sample A are discussed. © 2005 Wiley Periodicals, Inc. J Biomed Mater Res, 2005
In vivo evaluation of a porous hydroxyapatite/poly‐DL‐lactide composite for use as a bone substitute
Authors: Hasegawa Shin , Tamura Jiro , Neo Masashi , Goto Koji , Shikinami Yasuo , Saito Makoto , Kita Masakazu , Nakamura Takashi 
Published: August 2005

AbstractWe investigated the biocompatibility, osteoconductivity, and biodegradability of a porous composite of hydroxyapatite (HA) and poly‐DL‐lactide (PDLLA) implanted into rabbit femoral condyles and compared it with porous HA. Six weeks after implantation, the HA/PDLLA was covered with bone and contacted the bone directly. The amount of newly formed bone in the pores was similar in both materials during the examined period. The newly formed bone in the HA/PDLLA tended to increase over 26 weeks, but that in the HA did not show a significant increase after 12 weeks. By 26 weeks, remodeling of the newly formed bone in the pores was seen and bone marrow tissue was found in the pores of the HA/PDLLA. The porous HA/PDLLA was resorbed much faster than the porous HA. Porous HA/PDLLA was resorbed continuously through bone formation and remodeling. Conversely, porous HA was scarcely resorbed throughout the period. HA/PDLLA is thought to be degraded almost completely after about 1 year, and in this study, porous HA/PDLLA showed excellent osteoconductivity and faster resorption than HA. Therefore, HA/PDLLA might be a desirable material for bone substitutes. © 2005 Wiley Periodicals, Inc. J Biomed Mater Res, 2005
Fatigue of kidney stones with heterogeneous microstructure subjected to shock‐wave lithotripsy
Authors: Zohdi T. I. , Szeri A. J. 
Published: August 2005

AbstractIn this article a theoretical framework is developed for the mechanics of kidney stones with an isotropic, random microstructure—such as those comprised of cystine or struvite. The approach is based on a micromechanical description of kidney stones comprised of crystals in a binding matrix. Stress concentration functions are developed to determine load sharing of the particle phase and the binding matrix phase. Measurements have shown the inclusions to be considerably harder than the binder; consequently, loading of a stone leads to higher stresses in the inclusions than in the binder. As an illustration of the theory, the fatigue of kidney stones subject to shock‐wave lithotripsy is considered. Stress concentration functions are used to construct fatigue‐life estimates for each phase, as a function of the volume fraction and of the mechanical properties of the constituents, as well as the loading from SWL. The failure of the binding matrix, or of the particulate phase, is determined explicitly in a model for the accumulation of distributed damage. The theory can be used to assess the importance of microscale heterogeneity on the comminution of renal calculi, and to estimate the number of cycles to failure in terms of measurable material properties. © 2005 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2005
Prospects: Histone deacetylase inhibitors
Authors: Dokmanovic Milos , Marks Paul A. 
Published: August 2005

AbstractHistone deacetylase (HDAC), inhibitors represent a new class of targeted anti‐cancer agents. Several of these compounds are in clinical trials with significant activity against a spectrum of both hematologic and solid tumors at doses that are well tolerated by the patients. The HDAC inhibitors are a structurally diverse group of molecules that can induce growth arrest, differentiation, apoptosis, and autophagocytic cell death of cancer cells. While the base sequence of DNA provides the genetic code for proteins, the expression of genes is regulated, in large part, by the structure of the chromatin proteins around which the DNA is wrapped (epigenetic gene regulation). The acetylation and deacetylation of the lysines in the tails of the core histones, among the most extensively studied aspects of chromatin structure, is controlled by the action of two families of enzymes, histone deacetylases (HDACs) and histone acetyltransferases (HATs). Protein components of transcription factor complexes and many other non‐histone proteins are also substrates for HDACs and HATs. The structure and activity of these non‐histone proteins may be altered by acetylation/deacetylation with consequent effects on various cell functions including gene expression, cell cycle progression, and cell death pathways. This review focuses on several key questions with respect to the mechanism of action of HDACi, including, what are the different cell phenotypes induced by HDACi, why are normal cells compared to transformed cells relatively resistant to HDACi induced cell death, why are certain tumors more responsive to HDACi than others, and what is the basis of the selectivity of HDACi in altering gene expression. The answers to these questions will have therapeutic importance since we will identify targets for enhancing the efficacy and safety of HDACi. © 2005 Wiley‐Liss, Inc.
Upregulation of Daxx mediates apoptosis in response to oxidative stress
Authors: Kim Kyung Soon , Hwang Hyun‐Ah , Chae Suhn‐Kee , Ha Hyunjung , Kwon Ki‐Sun 
Published: August 2005

AbstractOxidative stress induces apoptosis in a variety of cell types by as yet unclear signaling mechanisms. The Daxx protein is reportedly involved in apoptosis through its interactions with Fas, transforming growth factor‐β receptor, and promyelocytic leukemia protein (PML). Here, we explored the possible roles of Daxx in oxidative stress‐induced apoptosis. We found that both the mRNA and protein levels of Daxx markedly increased when cells underwent apoptosis after H2O2 treatment. Pretreatment with the cell‐permeable antioxidant, N‐acetyl cysteine, prevented cells from H2O2‐induced Daxx upregulation and subsequent apoptosis, indicating that the endogenous oxidant regulated Daxx expression. Furthermore, suppression of endogenous Daxx expression by antisense oligonucleotide technology inhibited oxidative stress‐induced apoptosis in HeLa cells. Taken together, these results suggest that Daxx acts as an intermediary messenger of pro‐apoptotic signals triggered by oxidative stress. © 2005 Wiley‐Liss, Inc.
PIKE/nuclear PI 3‐kinase signaling in preventing programmed cell death
Authors: Ye Keqiang 
Published: August 2005

AbstractPI 3‐kinase enhancer (PIKE) is a nuclear GTPase that enhances PI 3‐kinase (PI3K) activity. Nerve growth factor (NGF) treatment leads to PIKE activation by triggering the nuclear translocation of PLC‐γ1, which acts as a physiological guanine nucleotide exchange factor (GEF) for PIKE. PI3K occurs in the nuclei of a broad range of cell types, and various stimuli elicit PI3K nuclear translocation. While cytoplasmic PI3K has been well characterized, little is known about the biological function of nuclear PI3K. Surprisingly, nuclei from 30 min NGF‐treated PC12 cells are resistant to DNA fragmentation initiated by the activated cell‐free apoptosome, and both PIKE and nuclear PI3K are sufficient and necessary for this effect. Moreover, pretreatment of the control nucleus with PI(3,4,5)P3 alone mimics the anti‐apoptotic activity of NGF by selectively preventing apoptosis, for which nuclear Akt is required but not sufficient. Recently, a nuclear PI(3,4,5)P3 receptor, nucleophosmin/B23, has been identified from NGF‐treated PC12 nuclear extract. PI(3,4,5)P3/B23 complex mediates the anti‐apoptotic effects of NGF by inhibiting DNA fragmentation activity of caspase‐activated DNase (CAD). Thus, PI(3,4,5)P3/B23 complex and nuclear Akt effectors might coordinately mediate PIKE/nuclear PI3K signaling in promoting cell survival by NGF. © 2005 Wiley‐Liss, Inc.
Stimulation of amphiregulin expression in osteoblastic cells by parathyroid hormone requires the protein kinase A and cAMP response element‐binding protein signaling pathway
Authors: Qin Ling , Partridge Nicola C. 
Published: August 2005

AbstractParathyroid hormone (PTH), an anabolic agent for bone metabolism, has profound effects on gene expression in the osteoblast. Recently, we identified that amphiregulin (AR), an EGF‐like ligand, is an immediate early gene for PTH treatment and has an important role in bone metabolism. In the present report, by using different PTH peptide fragments, protein kinase activators, and inhibitors, we have demonstrated that PTH regulates amphiregulin in a cAMP‐protein kinase A (PKA)‐dependent manner both in vitro and in vivo. We found that the phosphorylation of cAMP‐response element (CRE)‐binding protein (CREB) preceded AR transcription after PTH treatment. Moreover, luciferase reporter assays revealed that the binding of phosphorylated CREB to a conserved CRE site in the AR promoter plays an important role in basal, PTH‐induced, and prostaglandin E2 (PGE2)‐induced AR expression in osteoblastic cells. In summary, our data suggest that PTH‐induced AR mRNA expression is mediated primarily through cAMP‐PKA‐CREB signaling. © 2005 Wiley‐Liss, Inc.
Molecular markers in malignant cutaneous melanoma: Gift horse or one‐trick pony?
Authors: Martinez Steve R. , Hoon Dave S.B. 
Published: August 2005

AbstractThe management of malignant cutaneous melanoma is problematic. Current clinical prognostic factors do not adequately predict disease recurrence and overall survival in a significant subset of patients. Adjuvant therapies for melanoma are notoriously toxic and associated with significant morbidity. Furthermore, it has been difficult to predict which patients will respond best to these treatments, if at all. DNA and RNA biomarkers have been developed to help overcome these problems. Biomarkers have been shown to upstage patients with melanoma, but are the assays sensitive and specific enough for clinical use as predictors of disease outcome or treatment response? We review our experience with DNA and RNA biomarkers in terms of their prognostic and predictive capabilities in malignant melanoma and outline their likely role in the future of melanoma staging, surveillance, and treatment. © 2005 Wiley‐Liss, Inc.
TGF‐β control of cell proliferation
Authors: Huang Shuan S. , Huang Jung S. 
Published: August 2005

AbstractThis article focuses on recent findings that the type V TGF‐β receptor (TβR‐V), which co‐expresses with other TGF‐β receptors (TβR‐I, TβR‐II, and TβR‐III) in all normal cell types studied, is involved in growth inhibition by IGFBP‐3 and TGF‐β and that TGF‐β activity is regulated by two distinct endocytic pathways (clathrin‐ and caveolar/lipid‐raft‐mediated). TGF‐β is a potent growth inhibitor for most cell types, including epithelial and endothelial cells. The signaling by which TGF‐β controls cell proliferation is not well understood. Many lines of evidence indicate that other signaling pathways, in addition to the prominent TβR‐I/TβR‐II/Smad2/3/4 signaling cascade, are required for mediating TGF‐β‐induced growth inhibition. Recent studies revealed that TβR‐V, which is identical to LRP‐1, mediates IGF‐independent growth inhibition by IGFBP‐3 and mediates TGF‐β‐induced growth inhibition in concert with TβR‐I and TβR‐II. In addition, IRS proteins and a Ser/Thr‐specific protein phosphatase(s) are involved in the TβR‐V‐mediated growth inhibitory signaling cascade. The TβR‐V signaling cascade appears to cross‐talk with the TβR‐I/TβR‐II, insulin receptor (IR), IGF‐I receptor (IGF‐IR), integrin and c‐Met signaling cascades. Attenuation or loss of the TβR‐V signaling cascade may enable carcinoma cells to escape from TGF‐β growth control and may contribute to the aggressiveness and invasiveness of these cells via promoting epithelial‐to‐mesenchymal transdifferentiation (EMT). Finally, the ratio of TGF‐β binding to TβR‐II and TβR‐I is a signal controlling TGF‐β partitioning between two distinct endocytosis pathways and resultant TGF‐β responsiveness. These recent studies have provided new insights into the molecular mechanisms underlying TGF‐β‐induced cellular growth inhibition, cross‐talk between the TβR‐V and other signaling cascades, the signal that controls TGF‐β responsiveness and the role of TβR‐V in tumorigenesis. © 2005 Wiley‐Liss, Inc.
Differential regulation of cyclooxygenase 2 expression by small GTPases Ras, Rac1, and RhoA
Authors: Chang Yu‐Wen E. , Putzer Kevin , Ren Ling , Kaboord Barbara , Chance Terry W. , Qoronfleh M. Walid , Jakobi Rolf 
Published: August 2005

AbstractCyclooxygenase 2 (COX‐2) is an immediate early gene induced by a variety of stimuli and its expression is stimulated by individual activation of Ras or Rho GTPases. Here we investigate the role of coordinate activation of Ras and Rho GTPases in the induction of COX‐2. Individual expression of constitutively active Ras, RhoA, or Rac1 was capable of stimulating COX‐2 expression in NIH3T3 cells, but co‐expression of constitutively active RhoA with either constitutively active Ras or Rac1 was required for full stimulation of COX‐2 expression. Serum growth factors differentially activated Ras, RhoA, and Rac1, which correlated with the activation of Raf‐1, ERK, and c‐Jun as well as with induction of COX‐2. Inhibition of Ras significantly blocked the activation of Raf‐1, ERK, and c‐Jun and the stimulation of COX‐2 expression in response to serum. In contrast, inhibition of Rho family GTPases partially blocked serum induction of ERK activation but had little effects on COX‐2 expression. Both inhibitors of MEK (PD098059) and JNK (SP600125) inhibited serum induction of COX‐2. PD98059 only inhibited constitutively active Ras‐induced COX‐2 expression, while SP600125 significantly inhibited both constitutively active Ras‐ and RhoA‐induced COX‐2 expression. Together, our data suggest that constitutively active oncogenic Ras and Rho coordinately stimulate COX‐2 expression whereas transient activation of Ras but not RhoA or Rac1 mediates the induction of COX‐2 in response to serum. Furthermore, ERK and JNK activation are both required for serum‐ and oncogenic Ras‐mediated COX‐2 expression whereas only JNK activation is required for oncogenic RhoA‐mediated stimulation of COX‐2 expression. © 2005 Wiley‐Liss, Inc.
E2F1 induces cell death, calpain activation, and MDMX degradation in a transcription independent manner implicating a novel role for E2F1 in neuronal loss in SIV encephalitis
Authors: Strachan Gordon D. , Koike Maya A. , Siman Robert , Hall David J. , Jordan‐Sciutto Kelly L. 
Published: August 2005

AbstractThe E2F1 transcription factor can initiate proliferation or apoptosis, the latter by both transcription‐dependent and ‐independent mechanisms. Recently, an E2F1 mutant lacking the DNA binding domain, E2F1(180–437), has been implicated in degradation of MDMX and MDM2 proteins via lysosomal proteases. MDM proteins block p53 dependent apoptosis by directly inhibiting p53 stability and function. Here we demonstrate E2F1(180–437) induces death in HEK293 cells independent of E2F1 transcriptional activation and p53 stabilization. E2F1(180–437) elevates the activity of the calcium‐activated protease, calpain, which is required for E2F1 induced proteolysis of MDMX and E2F1 induced cell loss. To determine if E2F1 could be activating proteolysis via calpains in neurodegeneration, we examined MDMX immunofluorescence in simian immunodeficiency virus encephalitis (SIVE). We found a reciprocal relationship between E2F1 and MDMX staining: in SIVE where E2F1 immunostaining is increased, MDMX is decreased, while in controls where E2F1 immunostaining is low, MDMX is high. Together these experiments support a new function for E2F1 in the activation of calpain proteases and suggest a role for this pathway in SIVE. © 2005 Wiley‐Liss, Inc.
CH/π interactions involving aromatic amino acids: Refinement of the CHARMM tryptophan force field
Authors: Macias Alba T. , MacKerell Alexander D. 
Published: August 2005

AbstractHigh‐level ab initio calculations have been carried out to study weak CH/π interactions and as a check of the CHARMM force field for aromatic amino acids. Comparisons with published data indicate that the MP2/cc‐pVTZ level of theory is suitable for calculations of CH/π interaction, including the T‐shape benzene dimer. This level of theory was, therefore, applied to investigate CH/π interactions between ethene or cis‐2‐butene and benzene in a variety of orientations. In addition, complexes between ethene and a series of model compounds (toluene, methylindole and p‐cresol) representing the aromatic amino acids were studied motivated by the presence of CH/π interactions in biological systems. Ab initio binding energies were compared to the binding energies obtained with the CHARMM22 force field. In the majority of orientations, CHARMM22 reproduces the preferred binding modes, with excellent agreement for the benzene dimer. Small discrepancies found in the calculations involving methylindole along with a survey of published thermodynamic data for the aromatic amino acids prompted additional optimization of the tryptophan force field. Partial atomic charges, Lennard–Jones parameters, and force constants were improved to obtain better intra‐ and intermolecular properties, with significant improvements obtained in the reproduction of experimental heats of sublimation for indole and free energies of aqueous solvation for methylindole. © 2005 Wiley Periodicals, Inc. J Comput Chem 26: 1452–1463, 2005
Poverty reduction strategy papers and the fisheries sector: an opportunity forgone?
Authors: Thorpe Andy , Reid Chris , Anrooy Raymon Van , Brugere Cecile , Becker Denis 
Published: August 2005

AbstractThis article examines the extent to which the fisheries sector has been mainstreamed into the Poverty Reduction Strategy Papers (PRSPs) published by fifty nations by the end of 2003. Applying content analysis techniques we find that there is little overt relationship between the extent of such mainstreaming and the significance of the sector (as either a contributor to food security, a generator of foreign exchange, a provider of employment or as a refuge of the poor). Copyright © 2005 John Wiley & Sons, Ltd.
Simulation of capacitive array sensors using finite and infinite elements
Authors: Heyliger P. R. , Moulder J. C. , Nakagawa N. 
Published: August 2005

AbstractThe response of capacitive array sensors in the presence of flawed solid materials is simulated using finite elements and infinite elements with exponential decay. Conventional finite elements are used to model the critical regions near the probe and the surface of the solid. Infinite elements are used to represent the farfield conditions of the space surrounding the probe and the solid. The method is first applied to problems with analytic solutions to determine the accuracy of the results obtained using the infinite elements. The response of a capacitive array sensor is then simulated using a line integral which measures the relative change in admittance between flawed and unflawed solids. Examples of capacitive probe responses are given for several parametric variations of the flaw size and dielectric constant of the solid.
A new time‐domain transverse resonance method in solving guided wave problems
Authors: Kuo Chih‐Wen , Itoh Tatsuo 
Published: August 2005

AbstractA new time‐domain approach based on the frequency‐domain transverse resonance method is proposed to solve guided wave problems. This new method is capable of solving both the two‐dimensional and the three‐dimensional propagation problems. The structure under investigation is cut into individual substructures. Time‐domain Green's functions of each substructure are computed via the analytical inverse Laplace transform of the frequency‐domain Green's functions. The original problem is reconstructed by connecting the cut‐out substructures together through the interface boundary conditions. In order to verify the present approach, the empty rectangular waveguide is used as a comparison. With accurately calculated time‐domain Green's functions, the data obtained are in good agreement with the analytical results.