bluuebunny/crossref_metadata_2025_split huggingface dataset:
VPAC1 Expression Is Regulated by FXR Agonists in the Human Gallbladder Epithelium *
Authors: Chignard Nicolas , Mergey Martine , Barbu Véronique , Finzi Laetitia , Tiret Emmanuel , Paul Annick , Housset Chantal 
Published: July 2005

Abstract

Vasoactive intestinal peptide receptor-1 (VPAC1) is the high-affinity receptor of vasoactive intestinal peptide (VIP), a major regulator of bile secretion. To better define the level at which VPAC1 stimulates bile secretion, we examined its expression in the different cell types participating in bile formation (

i.e.

, hepatocytes, bile duct, and gallbladder epithelial cells). Because VPAC1 expression was previously shown to be regulated by nuclear receptors, we tested the hypothesis that it may be regulated by the farnesoid X receptor (FXR). Quantitative RT-PCR and immunoblot analyses of cell isolates indicated that VPAC1 is expressed in all three cell types lining the human biliary tree, with predominant expression in the gallbladder. In primary cultures of human gallbladder epithelial cells, VIP induced cAMP production and chloride secretion. Analysis of the VPAC1 gene revealed the presence of potential FXR response element sequences, and both FXR and RXRα expressions were detected in gallbladder epithelial cells. In these cells, the FXR pharmacological agonist GW4064 upregulated VPAC1 expression in a dose-dependent manner, and this effect was antagonized by the RXRα ligand, 9-cis retinoic acid. Chenodeoxycholate activated endogenous FXR in gallbladder epithelial cells, as ascertained by electromobility shift assay and upregulation of the FXR target gene, small heterodimer partner. Chenodeoxycholate also provoked an increase in VPAC1 mRNA and protein content in these cells.
In conclusion
, FXR agonists may increase gallbladder fluid secretion through transcriptional activation of VPAC1, which may contribute to the regulation of bile secretion by bile salts and to a protective effect of FXR pharmacological agonists in gallstone disease. (Hepatology 2005.)
Proteasome Inhibition Sensitizes Hepatocellular Carcinoma Cells, But Not Human Hepatocytes, to TRAIL *
Authors: Ganten Tom M. , Koschny Ronald , Haas Tobias L. , Sykora Jaromir , Li-Weber Min , Herzer Kerstin , Walczak Henning 
Published: July 2005

Abstract

TRAIL exhibits potent anti-tumor activity on systemic administration in mice. Because of its proven

in vivo

efficacy, TRAIL may serve as a novel anti-neoplastic drug. However, approximately half of the tumor cell lines tested so far are TRAIL resistant, and potential toxic side effects of certain recombinant forms of TRAIL on human hepatocytes have been described. Pretreatment with the proteasome inhibitor MG132 and PS-341 rendered TRAIL-resistant hepatocellular carcinoma (HCC) cell lines but not primary human hepatocytes sensitive for TRAIL-induced apoptosis. We investigated the different levels of possible MG132-induced interference with resistance to apoptotic signal transduction. Although proteasome inhibition efficiently suppressed nuclear factor-kappaB (NF-κB) activity, specific suppression of NF-κB by mutIκBα failed to sensitize TRAIL-resistant cell lines for TRAIL-induced apoptosis. In contrast to the previously reported mechanism of sensitization by 5-fluorouracil (5-FU), cellular FLICE-inhibitory protein (cFLIP)L and cFLIPS were markedly upregulated in the TRAIL death inducing signaling complex (DISC) by proteasome inhibitor pretreatment. Compared with 5-FU pretreatment, caspase-8 was more efficiently recruited to the DISC in MG132 pretreated cells despite the presence of fewer death receptors and more cFLIP in the DISC. But downregulation of cFLIP by short interference RNA (siRNA) further sensitized the HCC cell lines.
In conclusion
, these results show that otherwise chemotherapy-resistant tumor cells can be sensitized for TRAIL-induced apoptosis at the DISC level in the presence of high levels of cFLIP, which suggests the existence of an additional factor that modulates the interaction of FADD and the TRAIL death receptors. Of clinical relevance, proteasome inhibitors sensitize HCC cells but not primary human hepatocytes for TRAIL-induced apoptosis. (Hepatology 2005.)
LKM1 Autoantibodies in Chronic Hepatitis C Infection: A Case of Molecular Mimicry? *
Authors: Marceau Gabriel , Lapierre Pascal , Béland Kathie , Soudeyns Hugo , Alvarez Fernando 
Published: July 2005

Abstract

Anti-liver-kidney microsome type 1 (LKM1) autoantibodies directed against the cytochrome P450 2D6 (CYP2D6) are considered specific markers of type 2 autoimmune hepatitis, but are also found in 5% of sera from patients chronically infected by hepatitis C virus (HCV). Molecular mimicry between HCV proteins and CYP2D6 has been proposed to explain the emergence of these autoantibodies. Anti-LKM1 autoantibodies from hepatitis C–infected patients were affinity-purified against immobilized CYP2D6 protein and used to screen a phage display library. CYP2D6 conformational epitopes were identified using phage display analysis and the identification of statistically significant pairs (SSPs). Cross-reactivity between CYP2D6 and HCV protein candidates was tested by immunoprecipitation. Nineteen different clones were isolated, and their sequencing resulted in the mapping of a conformational epitope to the region of amino acids 254-288 of CYP2D6. Candidate HCV proteins for molecular mimicry included: core, E2, NS3 and NS5a. Affinity-purified autoantibodies from HCV+/LKM1+ patients immunoprecipitated either NS3, NS5a, or both, and these reactivities were specifically inhibited by immobilized CYP2D6.
In conclusion
, HCV+/LKM1+ sera recognize a specific conformational epitope on CYP2D6 between amino acids 254 to 288, the region that contains the major linear epitope in type 2 autoimmune hepatitis patients. Cross-reactivity due to molecular mimicry at the B-cell level was shown between the CYP2D6 and the HCV NS3 and NS5a proteins and could explain the presence of anti-LKM1 in patients chronically infected with HCV. Further investigation of the role played by this molecular mimicry in HCV-infected patients may lead to more specific strategies for diagnosis and treatment. (Hepatology 2005.)
Spectrum of NAFLD and Diagnostic Implications of the Proposed New Normal Range for Serum ALT in Obese Women *
Authors: Kunde Sachin S. , Lazenby Audrey J. , Clements Ronald H. , Abrams Gary A. 
Published: July 2005

Abstract

The upper limit of normal for ALT activity has been recommended to be lowered to ≤30 U/L in men and ≤19 U/L in women. These changes have been suggested to be diagnostically useful in subjects with nonalcoholic fatty liver disease (NAFLD). Our aim was to investigate the prevalence and spectrum of NAFLD with regard to the new ALT guidelines in 233 women with class II/III obesity. We compared our prior reference range for ALT (ULN ≤ 30 U/L in women) with the new standard. Our study demonstrates that only 86 patients (36.9%) would be classified as having normal ALT levels compared with 169 patients (72.5%) by the new and old standards, respectively. In patients with normal ALT activity (new vs. old standard), the prevalence of fatty liver (FL: 39.5% vs 40.2%), portal fibrosis, and steatosis (IPF: 37.2% vs. 33.7%) and nonalcoholic steatohepatitis (NASH: 23.3% vs. 26%) were similar. In comparison, newly defined patients with elevated ALT levels (>19 U/L) demonstrated an increased prevalence of FL (36%) and IPF (11.6%) but a 23.8% decrease in the prevalence of NASH as compared with the old standard. The sensitivity and specificity for NASH were 42% and 80% (ALT > 30 U/L) compared with 74% and 42% (ALT > 19 U/L).
In conclusion
, a significant increase in the prevalence of FL and IPF is detected in subjects with elevated ALT levels with the application of the new standard. However, the diagnostic utility for ALT to identify NASH or IPF remains poor, and significant healthcare expenditures may be incurred if this standard is adopted. (Hepatology 2005.)
Imparting mineral affinity to proteins with thiol–labile disulfide linkages
Authors: Bansal Geeti , Wright Jennifer E. I. , Zhang Sufeng , Zernicke Ronald F. , Uludag Hasan 
Published: July 2005

AbstractChemical conjugation of bisphosphonates (BPs) to proteins is an effective means to enhance binding of proteins to mineral‐containing biomaterials. BPs linked to proteins with reversible (i.e., cleavable) linkages were considered desirable over the conjugates linked with stable linkages because cleavable linkages allow protein release in free form from the mineral‐containing biomaterials. To explore the feasibility of creating cleavable BP‐protein conjugates, an amine‐ and a thiol‐containing BP were conjugated to the model protein Bovine Serum Albumin (BSA) with N‐succinimidyl‐3‐(2‐pyridyldithio)propionate (SPDP), which resulted in disulfide‐linked BP–BSA conjugates. Although disulfide‐linked conjugates were stable under aqueous conditions, the conjugates in solution were readily cleaved in the presence of physiological concentrations (∼ 0.3 mM) of the thiol compound, cysteine. The imparted mineral affinity as a result of BP conjugation, as assessed by hydroxyapatite (HA) binding in vitro, was lost upon cleavage of the disulfide‐linked BP. The conjugates bound to HA were also cleavable with cysteine, but their cleavage rate was significantly reduced as compared to the conjugates in solution. In conclusion, disulfide‐linked BP conjugates were shown to be readily cleavable by the amino acid cysteine and this resulted in the loss of imparted mineral affinity of the proteins. The proposed approach will be useful for modulating in vivo delivery of proteins implanted with mineral‐containing biomaterials. © 2005 Wiley Periodicals, Inc. J Biomed Mater Res, 2005
New experimental approach to study host tissue response to surgical mesh materials in vivo
Authors: Laschke M. W. , Häufel J. M. , Thorlacius H. , Menger M. D. 
Published: July 2005

AbstractImplantation of surgical meshes is a common procedure to increase abdominal wall stability in hernia repair. To improve biocompatibility of the implants, sophisticated in vivo animal models are needed to study inflammation and incorporation of biomaterials. Herein, we have established a new model that allows for the quantitative analysis of host tissue response and vascular ingrowth into surgical mesh materials in vivo. Ultrapro meshes were implanted into dorsal skinfold chambers of Syrian golden hamsters. Angiogenesis, microhemodynamics, microvascular permeability, and leukocyte–endothelial cell interaction of the host tissue were analyzed in response to material implantation over a 2‐week period using intravital fluorescence microscopy. Mesh implantation resulted in a short‐term activation of leukocytes, reflected by leukocyte accumulation and adherence in postcapillary venules. This cellular inflammatory response was accompanied by an increase of macromolecular leakage, indicating loss of integrity of venular endothelial cells. Angiogenesis started at day 3 after implantation by protrusion of capillary sprouts, originating from the host microvasculature. Until day 10, these sprouts interconnected with each other to form a new microvascular network. At day 14, the inflammatory response had disappeared and the vascular ingrowth was completed. Histology confirmed the formation of granulation tissue with adequate incorporation of the mesh filaments within the host tissue. We conclude that this novel model of surgical mesh implantation is a useful experimental approach to analyze host tissue response and vascular ingrowth of newly devised materials for hernia repair. © 2005 Wiley Periodicals, Inc. J Biomed Mater Res, 2005
The role of adsorbed fibrinogen in platelet adhesion to polyurethane surfaces: A comparison of surface hydrophobicity, protein adsorption, monoclonal antibody binding, and platelet adhesion
Authors: Wu Yuguang , Simonovsky Felix I. , Ratner Buddy D. , Horbett Thomas A. 
Published: July 2005

AbstractTen specially synthesized polyurethanes (PUs) were used to investigate the effects of surface properties on platelet adhesion. Surface composition and hydrophilicity, fibrinogen (Fg) and von Willebrand's factor (vWf) adsorption, monoclonal anti‐Fg binding, and platelet adhesion were measured. PUs preadsorbed with afibrinogenemic plasma or serum exhibited very low platelet adhesion, while adhesion after preadsorption with vWf deficient plasma was not reduced, showing that Fg is the key plasma protein mediating platelet adhesion under static conditions. Platelet adhesion to the ten PUs after plasma preadsorption varied greatly, but was only partially consistent with Fg adsorption. Thus, while very hydrophilic PU copolymers containing PEG that had ultralow Fg adsorption also had very low platelet adhesion, some of the more hydrophobic PUs had relatively high Fg adsorption but still exhibited lower platelet adhesion. To examine why some PUs with high Fg adsorption had lower platelet adhesion, three monoclonal antibodies (mAbs) that bind to sites in Fg thought to mediate platelet adhesion were used. The antibodies were: M1, specific to γ‐chain C‐terminal; and R1 and R2, specific to RGD containing regions in the α‐chain N‐ and C‐terminal, respectively. Platelet adhesion was well correlated with M1 binding, but not with R1 or R2 binding. When these mAbs were incubated with plasma preadsorbed surfaces, they blocked adhesion to variable degrees. The ability of the R1 and R2 mAbs to partially block adhesion to adsorbed Fg suggests that RGD sites in the alpha chain may also be involved in mediating platelet adhesion and act synergistically with the C‐terminal of the γ‐chain. © 2005 Wiley Periodicals, Inc. J Biomed Mater Res, 2005
Bioresorbable composites prepared by supercritical fluid foaming
Authors: Mathieu L. M. , Montjovent M.‐O. , Bourban P‐E. , Pioletti D. P. , Månson J.‐A. E. 
Published: July 2005

AbstractBone is a natural composite construct, with a gradient structure going from a loose interconnected cellular core to an outer dense wall, thus minimizing bone weight while keeping a high mechanical resistance. Due to this unique and complex structure, bone defects are difficult to replace or repair. Tissue engineering aims at providing artificial bone grafts. Several techniques have been proposed to produce porous structures or scaffolds, but, as yet, with no optimal solutions. This article focuses on bioresorbable ceramic–polymer composite foams obtained by supercritical fluid foaming. This flexible technique enables an adequate morphology and suitable properties for bone tissue engineering to be obtained. Composite scaffolds are biocompatible, allowing cell proliferation and differentiation. © 2005 Wiley Periodicals, Inc. J Biomed Mater Res, 2005
Thermogelling emulsions for vascular embolization and sustained release of drugs
Authors: Kan Pei , Lin Xi‐Zhang , Hsieh Ming‐Fa , Chang Ken‐Yuen 
Published: July 2005

AbstractThermogelling emulsion system was developed to function as an embolic agent and sustained release system. PEG‐PLGA‐PEG triblock copolymer was synthesized, and blended with oily phase (Lipiodol®) to constitute the thermogelling emulsions. Because the polymer‐rich aqueous phase dramatically increases viscosity in response to temperature change, especially within the range between 20 and 30°C, the emulsions produce a stop‐flowing gel with oil droplets entrapped. Thereafter, paclitaxels were released from the oily reservoir of gelled emulsions in a controlled manner. Reduced burst effect and steady drug release with near zero‐order release kinetics were observed. Human umbilical vein endothelial cells (HUVEC) were collected from fresh umbilical cords for in vitro antiangiogenesis test. It demonstrated that the sustained release of paclitaxel from emulsions inhibited growth of HUVEC and that the IC50, calculated according to release rate, was consistent with that obtained from free drug study. In addition, the emulsions forming a depot in situ inside the injection site of the blood vessel in rabbit ear obstructed the blood flow, and being monitored under X‐ray angiography. Taken together, this study proved the feasibility of the thermogelling emulsions for vascular embolization and sustained drug release. The results presented a potential system for arterial transcatheter embolization on hepatocellular carcinoma combined with antiangiogeneic treatment. © 2005 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2005
Degradation of poly‐L/DL‐lactide versus TCP composite pins: A three‐year animal study
Authors: Prokop Axel , Höfl Andreas , Hellmich Martin , Jubel Axel , Andermahr Jonas , Emil Rehm Klaus , Hahn Ulrich 
Published: July 2005

AbstractBiodegradable polylactide implants allow secure fixation of osteochondral fractures. This quasirandomized parallel‐group animal study investigates whether a composite implant of poly‐L/DL‐lactide (PLDLLA) with additional 10% β‐tricalcium phosphate produces an osteoconductive effect, whether the admixture positively influences implant degradation (assessed by comparing time to implant degradation), and whether the pin sites of degraded implants are replaced with bone tissue. On 36 medial femoral condyles of sheep, osteotomies were fixed with either three PLDLLA pins or three composite pins. At 3, 18, and 36 months, the pin sites were measured histologically and the state of degradation assessed according to Pistner's classification. All fractures healed without clinically relevant complications and without displacement. Both pin types led to asymptomatic pin‐site enlargement at 18 months, which disappeared by 36 months. At 18 months, 14 of 18 PLDLLA pins were no longer evident, whereas 16 of 18 composite pins showed only peripheral degradation. By 36 months, all implants from both groups were completely degraded and replaced with scar (2/18) or bone tissue (16/18). At 36 months there was no evidence for significant improvement of either degradation performance or osseointegration through use of the 10% TCP composite mixture. © 2005 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2005
Physiologically clotted fibrin‐calcined bone composite—A possible bone graft substitute
Authors: Noorjahan S. E. , Sastry T. P. 
Published: July 2005

AbstractFibrin plays a major role in blood clotting and is important in wound healing. In the present study, physiologically clotted fibrin (PF) and calcined bone (CB) both of bovine origin were used in the preparation of a bone graft material with chitosan (C) as a binder. This bone graft (PF‐CB) was characterized by stress‐strain analysis, X‐ray diffraction (XRD) studies, scanning electron microscopy, differential scanning calorimetry, thermogravimetric analysis, and FTIR spectroscopy. Thermal studies revealed that the incorporation of CB into PF did not alter the thermal stability of fibrin, although it affects the total loss percentage. The composition containing 24:1:15 (PF:C:CB) on dry weight basis exhibited maximum compressive strength, and the same composite was used for characterization studies. The XRD studies have shown the amorphous nature of the implant. SEM pictures revealed the heterogeneity and porous nature of the implant. PF in combination with CB is expected to exhibit osteoinductivity because fibrin, the osteoinductive protein, acts as an angiogenic factor, whereas CB provides calcium and phosphate ions that are needed for new bone formation. © 2005 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2005
Validation of a micro‐CT technique for measuring volumetric wear in retrieved acetabular liners
Authors: Bowden A. E. , Kurtz S. M. , Edidin A. A. 
Published: July 2005

AbstractIn this study, a novel micro‐CT–based technique for evaluating wear in retrieved acetabular liners was introduced and validated. Six UHMWPE acetabular components ranging in implantation time from 2.7 to 14.4 years were collected and evaluated with the use of a high‐resolution micro‐CT scanner. The components were scanned with a uniform volumetric resolution of 74 microns (16‐bit precision) with the use of a 1024 × 1024 in‐plane image matrix. Manual rigid 3D image registration of the interior hemispherical portion of the acetabular cup with geometric primitives by trained observers allowed for isolation, visualization, and measurement of the wear volume. Results for these six components indicated an average wear rate of 65 mm3/year. Overall scanner error was quantified gravimetrically and associated with a maximum uncertainty of 0.6%. Intra‐ and interobserver uncertainty analysis showed the method to be both accurate and repeatable. © 2005 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2005
Injectable gels of anionic collagen: Rhamsan composites for plastic correction: Preparation, characterization, and rheological properties
Authors: de Paula Márcio , Goissis Gilberto , Martins Virgínia C. A. , da Silva Trindade José Carlos 
Published: July 2005

AbstractThe present article describes the preparation and characterization of anionic collagen gels obtained from porcine intestinal submucosa after 72 h of alkaline treatment and in the form of rhamsan composites to develop injectable biomaterials for plastic reconstruction. All materials were characterized by SDS/polyacrylamide gel electrophoresis, infrared spectroscopy, thermal stability, potentiometric titration, rheological properties, and fluidity tests. Biocompatibility was appraised after the injection of anionic collagen:rhamsan composites at 2.5% in 60 North Folk rabbits. Independently of processing, the collagen's secondary structure was preserved in all cases, and after 72 h of hydrolysis the collagen was characterized by a carboxyl group content of 346 ± 9, which, at physiological pH, corresponds to an increase of 106 ± 17 negative charges, in comparison to native collagen, due to the selective hydrolysis of asparagine and glutamine carboxyamide side chain. Rheological studies of composites at pH 7.4 in concentrations of 2, 4, and 6% (in proportions of 75:1 and 50:1) showed a viscoelastic behavior dependent on the frequency, which is independent of concentration and proportion. In both, the concentration of the storage modulus always predominated over the loss modulus (G′ > G″ and δ < 45°). The results from creep experiments confirmed this behavior and showed that anionic collagen:rhamsan composites at pH 7.4 in the proportion of 50:1 are less elastic and more susceptible to deformation in comparison to gels in the proportion of 75:1, independent of concentration. This was further confirmed by flow experiments, indicating that the necessary force for the extrusion of anionic collagen:rhamsan composites, in comparison to anionic collagen, was significantly smaller and with a smooth flow. Biocompatibility studies showed that the tissue reaction of anionic collagen:rhamsan composites at 2.5% in the proportion of 75:1 was compatible with the application of these gels in plastic reconstruction. These results suggest that the association of collagen with rhamsan may be a good alternative in the replacement of glutaraldehyde to stabilize the microfibril assembly of commercial collagen gel preparations. © 2005 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2005