bluuebunny/crossref_metadata_2025_split huggingface dataset:
Structure–hepatoprotective activity relationship of 3,4‐dihydroxycinnamic acid (caffeic acid) derivatives
Authors: Pérez‐Alvarez V. , Bobadilla R. A. , Muriel P. 
Published: August 2002

Abstract3,4‐Dihydroxycinnamic acid (caffeic acid, CAF) is a natural product containing a catechol group with an α,β‐unsaturated carboxylic acid chain that has shown hepatoprotective properties. The aim of this work was to determine the importance of the 4‐hydroxy, 3‐hydroxy, 3,4‐dihydroxy substituents and the double bond moiety on the hepatic pharmacological effects of the molecule. We compared the ability of the caffeic, 4‐hydroxycinnamic, 3‐hydroxycinnamic, cinnamic and 3,4‐dihydroxyhydrocinnamic (a caffeic acid analogue without the double bond) acids at a dose of 50 mg kg−1, p.o., to reduce the liver damage produced by CCl4 (4 g kg−1, p.o.) intoxication in the rat. Cinnamic acid, the non‐hydroxylated analogue, only modestly protected the experimental animals challenged with CCl4, suggesting that hydroxyl groups participate in the pharmacological properties of CAF. The 3,4‐dihydroxyhydrocinnamic derivative did not show any significant differences when compared with the CAF effect in this model, suggesting that the double bond does not account for the liver pharmacological properties of CAF. In contrast, the 4‐hydroxy substituent seems to be very important for hepatoprotective activity because the 4‐hydroxy analogue improved almost every hepatic injury marker altered by CCl4, and in a better way than CAF did. Copyright © 2001 John Wiley & Sons, Ltd.
The porosity dependence of the dielectric constant for sintered hydroxyapatite
Authors: Hoepfner Timothy P. , Case Eldon D. 
Published: August 2002

AbstractHydroxyapatite (HAp) is the major mineral constituent of bone, and as such, the dielectric properties of HAp are of interest because electromagnetic fields have been shown to accelerate healing in bone fractures. In addition, an interest in the dielectric properties of HAp stems from the suggestion that electrically insulating HAp coatings might be used on implantable devices. In this study, the dielectric constant of polycrystalline hexagonal HAp was measured at nine different frequencies, from 45 kHz to 7.3 MHz for relative porosities ranging from 0.05 to 0.42. At a fixed frequency, the decrease in k as a function of increasing porosity is described well by an exponential function of porosity such that k = k0exp(−bP), where k0 is the dielectric constant at zero porosity and b is a constant. In addition, the entire data set of 108 data points (representing the 12 specimens of differing porosity measured at each of the nine frequencies) was fit to a candidate function formed from the product k0exp(−bP) and a simple expression relating frequency to the dielectric constant. The candidate function fit the data relatively well, with a coefficient of determination of 0.91. © 2002 Wiley Periodicals, Inc. J Biomed Mater Res 60: 643–650, 2002
Interaction of oxidation and crosslinking in gamma‐irradiated ultrahigh molecular‐weight polyethylene
Authors: Shen Fu‐Wen , McKellop Harry A. 
Published: August 2002

AbstractThe interaction between oxidation and crosslinking in gamma‐irradiated ultrahigh molecular‐weight polyethylene with and without artificial aging was studied. The effect of the atmosphere during irradiation (air vs. low oxygen) occurred primarily within about 0.5 mm of the surface, that is, the depth to which oxygen had diffused when the polyethylene specimen was machined and when it was irradiated. Irradiation in the presence of oxygen induced oxidation instead of crosslinking, so that the level of crosslinking achieved was lower than that which normally would occur at the same dose in the absence of oxygen. Subsequent artificial aging reduced the gel content (crosslinking) and had a maximal effect on the surface and subsurface regions for the gamma–air and gamma–low oxygen polyethylenes, respectively. Thus the storage environments and durations prior to irradiation and prior to artificial aging must be taken into account when attempting to duplicate the oxidation–crosslinking profiles that occur with actual implants in clinical use. In addition, the oxidation mechanisms initiated by the artificial aging method used in this study (i.e., heating in air to 80°C) initiated somewhat different oxidative reactions from those that occur during prolonged shelf life at room temperature or in vivo. In particular, the formation of a peak of oxidation below the free surface of the polyethylene is due to the combined effects of the distribution of residual free radicals and the diffusion gradient of the oxygen. The interactive relationship between oxidation and crosslinking characterized in the present study provides a fundamental basis for understanding the wear behavior of gamma‐sterilized components in past clinical use. It also provides guidelines for the development of polyethylenes with improved resistance to oxidation and wear, with particular relevance to estimation of the amount of crosslinking need‐ ed to potentially eliminate the clinical problem of osteolysis. © 2002 Wiley Periodicals, Inc. J Biomed Mater Res 61: 430–439, 2002
Adsorption and release properties of growth factors from biodegradable implants
Authors: Ziegler J. , Mayr‐Wohlfart U. , Kessler S. , Breitig D. , Günther K.‐P. 
Published: August 2002

AbstractThe present investigation was performed to study the adsorption behavior of growth factors and their release characteristics from biodegradable implants in an in vitro study. We investigated the stability of growth factors administered on various scaffolds. We used porous tricalcium phosphate ceramics (α‐TCP), a neutralized glass‐ceramics (GB9N), a composite (polylactid/‐glycolid/GB9N), and solvent dehydrated human bone as carriers. Block shaped scaffolds (sized: 7 × 7 × 10 mm) were loaded with 5 μg of either bone morphogenetic protein (rxBMP‐4), basic fibroblast growth factor (rh‐bFGF), or vascular endothelial growth factor (rh‐VEGF) solved in 150 μL PBS. The growth factors were labeled with Iodine125 (I‐125) for detecting the adsorbed and released amount of growth factors by counting the samples for total I‐125 activity. We observed that the adsorption of these growth factors seems to depend on two different parameters: first on the nature of the tested material, and second on the growth factors on their own. The release kinetics of the growth factors from the biodegradable implants can be described as a two phase process—a very rapid release during the first hours by an elution of not adsorbed protein, followed by a specific release, which depends upon the chemical/physical interaction of the material and the growth factor used. Analyzing the eluted proteins on SDS‐PAGEs rh‐VEGF was degraded into a smaller fragment with a size of around 15 kDa, while rxBMP‐4 and rh‐bFGF showed a complete degradation into fragments smaller than 3 kDa after more than 3 days. Although this in vitro study suggests that biodegradable implants might be successfully used as carriers for osteogenic growth factors, the different release kinetics as well as the alteration of their molecular structure including loss of biological activity should be considered. © 2001 Wiley Periodicals, Inc. J Biomed Mater Res 59: 422–428, 2002
Activation of a stress‐induced gene by insecticides in the midge, Chironomus yoshimatsui
Authors: Yoshimi Tatsuya , Minowa Kozue , Karouna‐Renier Natalie K. , Watanabe Chiharu , Sugaya Yoshio , Miura Takashi 
Published: August 2002

AbstractStress proteins (heat shock proteins, HSPs) have been proposed as general biomarkers for environmental monitoring. In the present study, we evaluated the environmental stress‐burden on the aquatic midge Chironomus yoshimatsui using hsp70 expression. Larvae collected from streams receiving polluted runoff (field strain) were resistant to the organophosphorus insecticide, fenitrothion (F), and the synthetic pyrethroid, ethofenprox (E), whereas a strain originally collected from an unpolluted area (susceptible strain) showed low resistance to insecticide exposure. To examine the expression of an HSP70 gene in C. yoshimatsui, an hsp70 cDNA probe was prepared using RNA obtained from the field strain larvae and used for Northern blot analyses. The expression of this HSP70 gene in larvae collected from two field sites in May about 1 week after insecticide spraying in the fields was 2.3 (p = 0.018) to 3.3 fold higher than that in the susceptible strain and was also 4.6 and 1.4 (p = 0.033) fold higher than those collected in November 3 months after the cessation of insecticide spraying. In order to identify potential inducers of the HSP70 gene of the field strain, larvae of the susceptible strain were exposed to F or E for 24 h and hsp70 mRNA levels determined. Exposures to F at 0.4 μg/L and E at 1.1 μg/L increased hsp70 mRNA levels 2.7 (p = 0.049) and 4.4 (p = 0.043) fold over controls, respectively. These results suggest that larvae collected from polluted areas are burdened by environmental stressors and the tested insecticides are potential inducers of HSP70. The results also support the suggestion that HSP70 gene expression is a sensitive indicator of low level (nonlethal) exposures to certain insecticides. © 2002 Wiley Periodicals, Inc. J Biochem Mol Toxicol 16:10–17, 2002; DOI 10.1002/jbt.10018
Effect of peroxisome proliferators on the methylation and protein level of the c‐myc protooncogene in B6C3F1 mice liver
Authors: Ge Rongrong , Tao Lianhui , Kramer Paula M. , Cunningham Michael L. , Pereira Michael A. 
Published: August 2002

AbstractPeroxisome proliferators in general are nongenotoxic mouse liver carcinogens for which DNA hypomethylation and altered gene expression are proposed mechanisms. Therefore, the peroxisome proliferators 2,4‐dichlorophenoxyacetic acid (2,4‐D), dibutyl phthalate (DBP), gemfibrozil, and Wy‐14,643 were evaluated for the ability to alter the methylation and expression of the c‐myc protooncogene. Male B6C3F1 mice were administered for 6 days in their diet Wy‐14,643 (5–500 ppm), 2,4‐D (1,680 ppm), DBP (20,000 ppm), or gemfibrozil (8,000 ppm). All four peroxisome proliferators caused hypomethylation of the c‐myc gene in the liver. Wy‐14,643 appeared to be the most efficacious with a threshold between 10 and 50 ppm. The level of the c‐myc protein was increased by Wy‐14,643, but not the other peroxisome proliferators. When female B6C3F1 mice received a two‐thirds partially hepatectomy and 16 h later were administered 50 mg/kg Wy‐14,643 by gavage, hypomethylation of the gene occurred 24 h later. Hypomethylation was not found in mice that received Wy‐14,643 following a sham operation. Hypomethylation of the c‐myc gene within 24 h of administering Wy‐14,643 after a partial hepatectomy but not after a sham operation supports the hypothesis that the peroxisome proliferators prevent methylation of hemimethylated sites formed by DNA replication. © 2002 Wiley Periodicals, Inc. J Biochem Mol Toxicol 16:41–47, 2002; DOI 10.1002/jbt.10019
The cellular prion protein: A new partner of the lectin CBP70 in the nucleus of NB4 human promyelocytic leukemia cells*
Authors: Rybner C. , Finel‐Szermanski S. , Felin M. , Sahraoui T. , Rousseau C. , Fournier J.‐G. , Sève A.‐P. , Botti J. 
Published: August 2002

AbstractPrion diseases are characterized by the presence of an abnormal isoform of the cellular prion protein (PrPc) whose physiological role still remains elusive. To better understand the function of PrPc, it is important to identify the different subcellular localization(s) of the protein and the different partners with which it might be associated. In this context, the PrPc–lectins interactions are investigated because PrPc is a sialoglycoprotein which can react with lectins which are carbohydrate‐binding proteins. We have previously characterized a nuclear lectin CBP70 able to recognize N‐acetyl‐β‐d‐glucosamine residues in HL60 cells. Using confocal immunofluorescence, flow‐cytofluorometry, and Western‐blotting, we have found that PrPc is expressed in the nucleus of the NB4 human promyelocytic leukemia cell line. It was also found that the lectin CBP70 is localized in NB4 cell nuclei. Moreover, several approaches revealed that PrPc and CBP70 are colocalized in the nucleus. Immunoprecipitation experiments showed that these proteins are coprecipitated and interact via a sugar‐dependent binding moiety. In conclusion, PrPc and CBP70 are colocalized in the nuclear compartment of NB4 cells and this interaction may be important to better understand the biological function and possibly the conversion process of PrPc into its pathological form (PrPsc). J. Cell. Biochem. 84: 408–419, 2002. © 2001 Wiley‐Liss, Inc.
Role of N‐cadherin‐ and integrin‐based costameres in the development of rat cardiomyocytes
Authors: Wu Jiahn‐Chun , Sung Hsin‐Ching , Chung Tun‐Hui , DePhilip Robert M. 
Published: August 2002

AbstractCostameres, vinculin‐containing structures found in skeletal and cardiac muscle, are thought to anchor the Z‐discs of the peripheral myofibrils to the sarcolemma. Several lines of evidence indicate that two different sets of costameres, integrin‐ and N‐cadherin‐based, are present in cardiac muscles. In this study, immunoblot analysis was used to study the expression of N‐cadherin, α‐catenin, β‐catenin, vinculin, talin, and laminin in rat cardiac muscles at embryonic days 15 and 19, the day of birth (postnatal day 0), postnatal weeks 1, 2, 3, and 4, and in the adult. Double immunofluorescence microscopy was performed to study the spatial and temporal distribution of these two sets of costameres in rat cardiomyocytes. Costameric staining for N‐cadherin, codistributed with β‐catenin, was strong from embryonic day 15 up to postnatal week 2, gradually decreased after postnatal week 3, and was undetectable at postnatal week 4 and in the adult. Confocal microscopy showed that N‐cadherin colocalized with α‐actinin at cortical myofibrils. Double‐labeling of β‐catenin and talin indicated the coexistence of N‐cadherin/catenin‐ and integrin/talin‐based costameres in rat cardiac muscle. Although β‐catenin and vinculin were co‐localized at the costamere of cardiomyocytes from embryonic day 15 to postnatal week 3, staining for β‐catenin or talin was mutually exclusive at all stages examined. These results demonstrate the simultaneous, but mutually exclusive, existence of N‐cadherin/catenin‐ and integrin/talin‐based costameres in rat cardiomyocytes between late embryonic stages and postnatal week 3, while only integrin/talin‐based costameres were found in adult rats. The N‐cadherin/catenin‐based costameres in rat cardiac muscles may play a role in myofibrillogenesis similar to that of their counterparts in cultured cardiomyocytes. J. Cell. Biochem. 84: 717–724, 2002. © 2002 Wiley‐Liss, Inc.
Isolation of baculovirus‐expressed human vitamin D receptor: DNA responsive element interactions and phosphorylation of the purified receptor
Authors: Jurutka Peter W. , MacDonald Paul N. , Nakajima Shigeo , Hsieh Jui‐Cheng , Thompson Paul D , Whitfield G. Kerr , Galligan Michael A. , Haussler Carol A. , Haussler Mark R. 
Published: August 2002

AbstractTwo controversial aspects in the mechanism of human vitamin D receptor (hVDR) action are the possible significance of VDR homodimers and the functional role of receptor phosphorylation. To address these issues, milligram quantities of baculovirus‐expressed hVDR were purified to 97% homogeneity, and then tested for binding to the rat osteocalcin vitamin D responsive element (VDRE) via electrophoretic mobility shift and half‐site competition assays in the presence or absence of a CV‐1 nuclear extract containing retinoid X receptor (RXR). Methylation interference analysis revealed that both the hVDR homodimer and the VDR‐RXR heterodimer display similar patterns of VDRE G‐base protection. However, in competition studies, the relative dissociation of the homodimeric hVDR complex from the VDRE was extremely rapid (t1/2 < 30 s) compared to the dissociation of the heteromeric complex (t1/2 > 5 min), thus illustrating the relative instability and low affinity of homodimeric VDR binding to DNA. These results indicate that VDR‐RXR heterodimers are the preferred VDRE binding species. Further, two dimensional gel electrophoresis of hVDR demonstrated several isoelectric forms of the receptor, suggesting that it is subject to multiple phosphorylation events. In vitro kinase assays confirmed that purified hVDR is an efficient substrate for protein kinases A and Cβ, as well as casein kinase II. In vivo studies of the expressed receptor in intact cells, namely baculovirus vector infected Sf9 insect cells and transfected mammalian COS‐7 cells, demonstrated that hVDR was phosphorylated in a hormone‐enhanced fashion. Functional consequences of hVDR phosphorylation were suggested by the observations that: (i) potato acid phosphatase (PAP)‐treated hVDR no longer interacted with the VDRE as either a homodimer or a heteromeric complex with RXR, and (ii) treatment of transfected COS‐7 cells with a phosphatase inhibitor (okadaic acid) along with 1,25‐dihydroxyvitamin D3 (1,25(OH)2D3) resulted in a synergistic enhancement of both hVDR phosphorylation and transactivation of a VDRE‐linked reporter gene, compared to the effect of treatment with either agent alone. These studies point to a significant role for phosphorylation of VDR in regulating high‐affinity VDR‐RXR interactions with VDREs, and also in modulating 1,25(OH)2D3‐elicited transcriptional activation in target cells. J. Cell. Biochem. 85: 435–457, 2002. © 2002 Wiley‐Liss, Inc.
Role of mTOR in the degradation of IRS‐1: Regulation of PP2A activity
Authors: Hartley David , Cooper Geoffrey M. 
Published: August 2002

AbstractWe have investigated the role of PI 3‐kinase and mTOR in the degradation of IRS‐1 induced by insulin. Inhibition of mTOR with rapamycin resulted in approximately 50% inhibition of the insulin‐induced degradation of IRS‐1. In contrast, inhibition of PI‐3 kinase, an upstream activator of mTOR, leads to a complete block of the insulin‐induced degradation. Inhibition of either PI‐3 kinase or mTOR prevented the mobility shift in IRS‐1 in response to insulin, a shift that is caused by Ser/Thr phosphorylation. These results indicate that insulin stimulates PI 3‐kinase‐mediated degradation of IRS‐1 via both mTOR‐dependent and ‐independent pathways. Platelet‐derived growth factor (PDGF) stimulation leads to a lower level of degradation, but significant phosphorylation of IRS‐1. Both the degradation and phosphorylation of IRS‐1 in response to PDGF are completely inhibited by rapamycin, suggesting that PDGF stimulates IRS‐1 degradation principally via the mTOR‐dependent pathway. Inhibition of the serine/threonine phosphatase PP2A with okadaic acid also induced the phosphorylation and degradation of IRS‐1. IRS‐1 phosphorylation and degradation in response to okadaic acid were not inhibited by rapamycin, suggesting that the action of mTOR in the degradation of IRS‐1 results from inhibition of PP2A. Consistent with this, treatment of cells with rapamycin stimulated PP2A activity. While the role of mTOR in the phosphorylation of IRS‐1 appears to proceed primarily through the regulation of PP2A, we also provide evidence that the regulation of p70S6 kinase phosphorylation requires the direct activity of mTOR. J. Cell. Biochem. 85: 304–314, 2002. © 2002 Wiley‐Liss, Inc.
Characterization of a 150 kDa accessory receptor for TGF‐β1 on keratinocytes: Direct evidence for a GPI anchor and ligand binding of the released form
Authors: Tam B.Y.Y. , Larouche D. , Germain L. , Hooper N.M. , Philip A. 
Published: August 2002

AbstractTransforming growth factor‐β (TGF‐β) is a key modulator of epidermal development and homeostasis, and has been shown to potently regulate keratinocyte migration and function during wound repair. There are three cloned TGF‐β receptors termed type I, type II, and type III that are found on most cell types. The types I and II are the signaling receptors, while the type III is believed to facilitate TGF‐β binding to the types I and II receptors. Recently, we reported that in addition to these receptors, human keratinocytes express a 150 kDa TGF‐β1 binding protein (r150) which forms a heteromeric complex with the TGF‐β signaling receptors. This accessory receptor was described as glycosyl phosphatidylinositol‐specific anchored based on its sensitivity to phosphatidylinositol phospholipase C (PIPLC). In the present study, we demonstrate that the GPI‐anchor is contained in r150 itself and not on a tightly associated protein and that it binds TGF‐β1 with an affinity similar to those of the types I and II TGF‐β signaling receptors. Furthermore, the PIPLC released (soluble) form of this protein is capable of binding TGF‐β1 independently from the signaling receptors. In addition, we provide evidence that r150 is released from the cell surface by an endogenous phospholipase C. Our observation that r150 interacts with the TGF‐β signaling receptors, together with the finding that the soluble r150 binds TGF‐β1 suggest that r150 in either its membrane anchored or soluble form may potentiate or antagonize TGF‐β signaling. Elucidating the mechanism by which r150 functions as an accessory molecule in TGF‐β signaling may be critical to understanding the molecular mechanisms underlying the regulation of TGF‐β action in keratinocytes. J. Cell. Biochem. 83: 494–507, 2001. © 2001 Wiley‐Liss, Inc.
Cloning and characterization of human syndecan‐3*
Authors: Berndt Christine , Casaroli‐Marano Ricardo P. , Vilaró Senén , Reina Manuel 
Published: August 2002

AbstractSyndecans are cell‐surface heparan sulfate proteoglycans, which perform a variety of functions in the cell. Most important, they are co‐receptors for growth factors and mediate cell–cell and cell–matrix interactions. Four syndecans (syndecan 1–4) have been described in different species. The aim of this work was the cloning and characterization of human syndecan‐3. The human syndecan‐3 sequence has high homology to the rat and mouse sequences, with the exception of the 5′‐region. Syndecan‐3 mRNA is mostly expressed in the nervous system, the adrenal gland, and the spleen. When different cell lines were transiently transfected with full‐length syndecan‐3 cDNA, it was localized to the membrane and induced the formation of long filopodia‐like structures, microspikes, and varicosities. Consequently, the actin cytoskeleton was re‐organized, since actin staining was mostly found in the cellular extensions and at the cell periphery, co‐localizing with the syndecan‐3 staining. The development of the phenotype depended on the presence of sugar chains, as transfected glycosaminoglycan‐deficient Chinese hamster ovary (CHO) 745 cells did not show these structural changes, nor did transfected CHO K1 cells in the presence of heparin. The similarity of the cloned DNA sequence with that of other mammalian species and the high expression in the nervous system led us to the assumption that human syndecan‐3 could perform comparable functions to those described for syndecan‐3 in rat and mouse. Additionally, transient transfection experiments suggest a role of human syndecan‐3 in the organization of cell shape by affecting the actin cytoskeleton, possibly by transferring signals from the cell surface in a sugar‐dependent mechanism. J. Cell. Biochem. 82: 246–259, 2001. © 2001 Wiley‐Liss, Inc.