bluuebunny/crossref_metadata_2025_split huggingface dataset:
Treatment of chronic hepatitis C in hemodialysis patients
Authors: Berenguer Marina 
Published: July 2008

Abstract

Hepatitis C virus (HCV) infection is especially problematic in patients with end-stage renal disease (ESRD) who are undergoing hemodialysis. Rates of HCV infection are higher among hemodialysis patients than in the general population, and several routes of transmission are thought to stem from the dialysis unit. Management of chronic hepatitis C is also more complicated in hemodialysis patients because of altered pharmacokinetics and a predisposition for drug-related toxicity, particularly ribavirin-induced anemia. Clinical trials of patients with chronic hepatitis C and healthy, functioning kidney grafts are rare because of the inherent dangers of graft rejection. As a result, most studies in patients with ESRD have focused on patients waiting for a kidney transplant. Additionally, because ribavirin is contraindicated in this patient population, many studies have examined monotherapy treatments. According to meta-analyses, conventional interferon alfa treatment yields a sustained virological response (SVR) rate of 37%, whereas studies of pegylated interferon alfa monotherapy have yielded SVR rates between 13% and 75%. Several small studies have also used the monitoring of ribavirin plasma concentrations or hemoglobin levels to facilitate the use of combination therapy. In light of the results from these clinical trials, we herein review treatment guidelines and recommend strategies to help optimize the treatment of patients with ESRD.

Conclusion:

There remains a lack of clarity surrounding the most effective treatment options for patients with chronic hepatitis C and ESRD. Treatment can be effective with many patients attaining SVR; however, unfavorable tolerability with interferon alfa–based therapy remains a concern and thus close supportive care should be aggressively pursued to help maintain adherence. (Hepatology 2008;48:1690–1699.)
Anti-CD81 antibodies can prevent a hepatitis C virus infection in vivo
Authors: Meuleman Philip , Hesselgesser Joseph , Paulson Matthew , Vanwolleghem Thomas , Desombere Isabelle , Reiser Hans , Leroux-Roels Geert 
Published: July 2008

Abstract

The viral life cycle of the hepatitis C virus (HCV) has been studied mainly using different

in vitro

cell culture models. Studies using pseudoviral particles (HCVpp) and more recently cell culture–derived virus (HCVcc) suggest that at least three host cell molecules are important for HCV entry

in vitro

: the tetraspanin CD81, the scavenger receptor class B member I, and the tight junction protein Claudin-1. Whether these receptors are equally important for an

in vivo

infection remains to be demonstrated. We show that CD81 is indispensable for an authentic

in vivo

HCV infection. Prophylactic treatment with anti-CD81 antibodies completely protected human liver-uPA-SCID mice from a subsequent challenge with HCV consensus strains of different genotypes. Administration of anti-CD81 antibodies after viral challenge had no effect.

Conclusion:

Our experiments provide evidence for the critical role of CD81 in a genuine HCV infection

in vivo

and open new perspectives for the prevention of allograft reinfection after orthotopic liver transplantation in chronically infected HCV patients. (Hepatology 2008;48:1761–1768.)
Naturally occurring dominant resistance mutations to hepatitis C virus protease and polymerase inhibitors in treatment-naïve patients
Authors: Kuntzen Thomas , Timm Joerg , Berical Andrew , Lennon Niall , Berlin Aaron M. , Young Sarah K. , Lee Bongshin , Heckerman David , Carlson Jonathan , Reyor Laura L. , Kleyman Marianna , McMahon Cory M. , Birch Christopher , Schulze zur Wiesch Julian , Ledlie Timothy , Koehrsen Michael , Kodira Chinnappa , Roberts Andrew D. , Lauer Georg M. , Rosen Hugo R. , Bihl Florian , Cerny Andreas , Spengler Ulrich , Liu Zhimin , Kim Arthur Y. , Xing Yanming , Schneidewind Arne , Madey Margaret A. , Fleckenstein Jaquelyn F. , Park Vicki M. , Galagan James E. , Nusbaum Chad , Walker Bruce D. , Lake-Bakaar Gerond V. , Daar Eric S. , Jacobson Ira M. , Gomperts Edward D. , Edlin Brian R. , Donfield Sharyne M. , Chung Raymond T. , Talal Andrew H. , Marion Tony , Birren Bruce W. , Henn Matthew R. , Allen Todd M. 
Published: July 2008

Abstract

Resistance mutations to hepatitis C virus (HCV) nonstructural protein 3 (NS3) protease inhibitors in <1% of the viral quasispecies may still allow >1000-fold viral load reductions upon treatment, consistent with their reported reduced replicative fitness

in vitro

. Recently, however, an R155K protease mutation was reported as the dominant quasispecies in a treatment-naïve individual, raising concerns about possible full drug resistance. To investigate the prevalence of dominant resistance mutations against specifically targeted antiviral therapy for HCV (STAT-C) in the population, we analyzed HCV genome sequences from 507 treatment-naïve patients infected with HCV genotype 1 from the United States, Germany, and Switzerland. Phylogenetic sequence analysis and viral load data were used to identify the possible spread of replication-competent, drug-resistant viral strains in the population and to infer the consequences of these mutations upon viral replication

in vivo

. Mutations described to confer resistance to the protease inhibitors Telaprevir, BILN2061, ITMN-191, SCH6 and Boceprevir; the NS5B polymerase inhibitor AG-021541; and to the NS4A antagonist ACH-806 were observed mostly as sporadic, unrelated cases, at frequencies between 0.3% and 2.8% in the population, including two patients with possible multidrug resistance. Collectively, however, 8.6% of the patients infected with genotype 1a and 1.4% of those infected with genotype 1b carried at least one dominant resistance mutation. Viral loads were high in the majority of these patients, suggesting that drug-resistant viral strains might achieve replication levels comparable to nonresistant viruses

in vivo

.

Conclusion:

Naturally occurring dominant STAT-C resistance mutations are common in treatment-naïve patients infected with HCV genotype 1. Their influence on treatment outcome should further be characterized to evaluate possible benefits of drug resistance testing for individual tailoring of drug combinations when treatment options are limited due to previous nonresponse to peginterferon and ribavirin. (Hepatology 2008;48:1769–1778.)
Cell culture–produced hepatitis C virus does not infect peripheral blood mononuclear cells
Authors: Marukian Svetlana , Jones Christopher T. , Andrus Linda , Evans Matthew J. , Ritola Kimberly D. , Charles Edgar D. , Rice Charles M. , Dustin Lynn B. 
Published: July 2008

Abstract

Hepatitis C virus (HCV) replicates primarily in the liver, but HCV RNA has been observed in association with other tissues and cells including B and T lymphocytes, monocytes, and dendritic cells. We have taken advantage of a recently described, robust system that fully recapitulates HCV entry, replication and virus production in vitro to re-examine the issue of HCV infection of blood cell subsets. The HCV replicase inhibitor 2′C-methyl adenosine was used to distinguish HCV RNA replication from RNA persistence. Whereas cell culture–grown HCV replicated in Huh-7.5 hepatoma cells, no HCV replication was detected in B or T lymphocytes, monocytes, macrophages, or dendritic cells from healthy donors. No blood cell subset tested expressed significant levels of Claudin-1, a tight junction protein needed for HCV infection of Huh-7.5 cells. A B cell line expressing high levels of Claudin-1, CD81, and scavenger receptor BI remained resistant to HCV pseudoparticle infection. We bypassed the block in HCV entry by transfecting HCV RNA into blood cell subsets. Transfected RNA was not detectably translated and induced high levels of interferon-α. Supernatants from HCV RNA–transfected macrophages inhibited HCV replication in Huh-7.5 cells.

Conclusion:

We conclude that multiple blocks prevent blood cells from supporting HCV infection. (Hepatology 2008;48:1843-1850.)
Ab initio simulation of the IR spectra of pyrope, grossular, and andradite
Authors: Zicovich‐Wilson C. M. , Torres F. J. , Pascale F. , Valenzano L. , Orlando R. , Dovesi R. 
Published: July 2008

AbstractIR spectra of pyrope Mg3Al2Si3O12, grossular Ca3Al2Si3O12 and andradite Ca3Fe2Si3O12 garnets were simulated with the periodic ab initio CRYSTAL code by adopting an all‐electron Gaussian‐type basis set and the B3LYP Hamiltonian. Two sets of 17 F1u Transverse Optical (TO) and Longitudinal Optical (LO) frequencies were generated, together with their intensities. Because the generation of LO modes requires knowledge of the high frequency dielectric constant ε∞ and Born effective charges, they were preliminary evaluated by using a finite field saw‐tooth model and well localized Wannier functions, respectively. As a by‐product, the static dielectric constant ε0 was also obtained. The agreement of the present calculated wavenumbers (i.e. peak positions) with the available experimental data is excellent, in that the mean absolute difference for the full set of data smaller than 8 cm−1. Missing peaks in experimental spectra were found to correspond to modes with low calculated intensities. Correspondence between TO and LO modes was established on the basis of the overlap between the eigenvectors of the two sets and similarity of isotopic shifts; as result, the so called LO‐TO splitting could be determined. Animation of the normal modes was employed to support the proposed pairing. © 2008 Wiley Periodicals, Inc. J Comput Chem, 2008
Interactions between an Anticancer Drug and Polymeric Micelles Based on Biodegradable Polyesters
Authors: Yang Xiaoqiang , Zhu Bo , Dong Tungalag , Pan Pengju , Shuai Xintao , Inoue Yoshio 
Published: July 2008

AbstractInteractions between the anticancer drug quercetin and biodegradable polyesters within micelles were investigated by DSC, WAXD, and UV analyses. For micelles based on poly(ethylene glycol) methyl ether‐block‐poly(ε‐caprolactone) (MPEG‐PCL), DSC analysis indicated that the interactions were between the hydrophobic core and the drug within the micelle. For micelles based on poly(ethylene glycol) methyl ether‐block‐poly(L‐lactide) (MPEG‐PLLA), the interactions were between the hydrophobic core and the drug and between hydrophilic segments and the drug. WAXD results indicated that no crystalline phase of the drug was found in either of the micelle types. Based on the DSC and WAXD results, two probable micelle structures were proposed. The UV spectra revealed the presence of hydrogen bonding as the main interaction between the drug and the polyesters.In vitrostudies demonstrated that quercetin release from micelles was sustained and was affected by the polymer–drug interaction.magnified image
Field‐Driven Surface Segregation of Biofunctional Species on Electrospun PMMA/PEO Microfibers
Authors: Sun Xiao‐Yu , Nobles Larrisha R. , Börner Hans G. , Spontak Richard J. 
Published: July 2008

AbstractThe need to biofunctionalize polymer surfaces for targeted bio‐related applications continues to grow, and efforts designed to meet this need rely heavily on surface grafting or polymerization. In this study, we provide a viable alternative by demonstrating that the peptide segment of a polymer‐peptide conjugate can be selectively driven to the surface of polymer nano/microfibers during electrospinning due to contrast in polarizability. Judicious choice of the polymer sequence in the conjugate permits use of the conjugate with compatible fiber‐forming polymers. Here, we use a water soluble poly(ethylene oxide)‐containing conjugate in combination with a hydrophobic thermoplastic, poly(methyl methacrylate). Surface enrichment is measured by X‐ray photoelectron spectroscopy, and fiber morphology is investigated by electron microscopy. Microfibers generated from the blends examined here are largely resistant to long term water immersion and are thus suited as support scaffolds or filtration membranes.magnified image
Novel zein‐based electrospun fibers with the water stability and strength necessary for various applications
Authors: Xu Weijie , Karst David , Yang Wen , Yang Yiqi 
Published: July 2008

AbstractBACKGROUND: Some of the problems with electrospun zein fiber are that it has very low tenacities in the dry and wet states and that mats of the fiber become films when immersed in water. The fibers are therefore unusable for various applications despite their good biocompatibility and biodegradability. This research was conducted to overcome these problems by electrospinning novel fibers containing various concentrations of zein, citric acid (CA) and sodium hypophosphite monohydrate (SHP) and by crosslinking the zein with CA and with SHP serving as a catalyst.RESULTS: The CA‐crosslinked electrospun zein fiber has as much as 10‐fold greater wet tenacity and 15‐fold greater dry tenacity than regular electrospun zein fiber. The average diameter of these fibers is 451 nm, which is the smallest diameter ever reported for zein‐based electrospun fiber. A mat of this fiber retains its fibrous structure when immersed in water, and the fiber retains about 70% of its tenacity after 16 days at 50 °C and 90% relative humidity.CONCLUSION: The high dry and wet tenacities, good water stability and small diameter of the novel CA‐crosslinked electrospun zein fiber make it attractive for biomedical and other applications that expose zein to water or that require high surface area. Copyright © 2008 Society of Chemical Industry
Chitosan enhances disease resistance in pearl millet against downy mildew caused by Sclerospora graminicola and defence‐related enzyme activation
Authors: Manjunatha G , Roopa KS , Prashanth Geetha N , Shekar Shetty H 
Published: July 2008

AbstractBACKGROUND: The present study investigated the effect of chitosan seed priming on the induction of disease resistance in pearl millet against downy mildew disease caused by Sclerospora graminicola (Sacc.) Schroet.RESULTS: Pearl millet seeds were primed with chitosan at different concentrations: 0.5, 1.5, 2.5 and 3 g kg−1 seed. Of the different concentrations, 2.5 g kg−1 was found to be optimum, with enhanced seed germination of 99% and seedling vigour of 1782, whereas the untreated control recorded values of 87% and 1465 respectively. At optimum concentration, chitosan did not inhibit sporulation and release of zoospores from sporangia. Furthermore, pearl millet seedlings raised after seed treatment with chitosan showed an increased level of the defence‐related enzymes chitosanase and peroxidase as compared with the untreated pearl millet seedlings on downy mildew pathogen inoculation. The effect of chitosan in reducing downy mildew incidence was evaluated in both greenhouse and field conditions, in which respectively 79.08 and 75.8% disease protection was obtained.CONCLUSION: Chitosan was effective in protecting pearl millet plants against downy mildew under both greenhouse and field conditions by inducing resistance against the pathogen. Thus, chitosan formulation can be recommended for seed treatment in the management of downy mildew disease. Copyright © 2008 Society of Chemical Industry
Resource‐dependent reproductive adjustment and the stability of consumer‐resource dynamics
Authors: Nakazawa Takefumi , Ohgushi Takayuki , Yamamura Norio 
Published: July 2008

AbstractThis study explored a consumer‐resource model including reproductive and nonreproductive subpopulations of the consumer to consider whether resource‐dependent reproductive adjustment by the consumer would stabilize consumer‐resource dynamics. The model assumed that decreasing (increasing) resource availability caused reproductive suppression (facilitation), and that the reproductive consumer had a higher mortality rate than the nonreproductive one (i.e., a trade‐off between reproduction and survival). The model predicted that the variability would be reduced when the consumer had a strong tendency to suppress reproduction in response to low resource availability or when the cost of reproduction was high, although consumer extinction became more likely. Furthermore, when the consumer‐resource dynamics converged to limit cycles, reproductive adjustment enhanced the long‐term average of the consumer density. It was also predicted that if reproductive suppression enhanced resource consumption efficiency (i.e., a trade‐off between reproduction and foraging), then it would destabilize the system by canceling the stabilizing effect of the reproductive adjustment itself. These results suggest that it is necessary not only to identify the costs of reproduction, but also to quantify the changes in individual‐level performances due to reproduction in order to understand the ecological consequences of reproductive adjustment.
Downregulation of cyclin D1‐CDK4 protein in human embryonic lung fibroblasts (HELF) induced by silica is mediated through the ERK and JNK pathway
Authors: Shen Fuhai , Fan Xueyun , Liu Bingci , Jia Xiaowei , Gao Ai , Du Hongju , Ye Meng , You Baorong , Huang Chuanshu , Shi Xianglin 
Published: July 2008

AbstractSilica is a factor in the induction of acute injury and chronic pulmonary fibrosis. In 1996, silica was also listed as a human carcinogen by the International Agency for Research on Cancer (IARC). However, the molecular mechanisms involved in its pathologic effects are not well understood. We found that exposure of human embryonic lung fibroblasts (HELF) to crystalline silica for 2 h decreased cyclin D1 and cyclin‐dependent kinase 4 (CDK4) expression levels. Extracellular signal‐regulated protein kinase (ERKs), c‐Jun NH2‐terminal amino kinase (JNKs), and p38 kinase, as well as their downstream transcription factor, AP‐1, had different effects on the regulation of expression levels of cyclin D1 and CDK4 alterations induced by silica.Silica activates multiple signal transduction pathways involved in coordinating cellular responses to stress. We established the requirements for ERK and JNK, members of the mitogen‐activated protein kinase (MAPK) family, in mediating G1 phase arrest of HELF induced by silica. Silica treatment activated ERK in a dose‐dependent manner. AG126 (a chemical inhibitor of the ERK signaling pathway) and the dominant negative mutant of ERK2 (a molecular inhibitor of ERK2) prevented decreases in cyclin D1 and CDK4 expression levels. A chemical inhibitor of JNK, SP600125, prevented the decreased expression of both cyclin D1 and CDK4, whereas SB203580, a chemical inhibitor of p38, did not. Interestingly, curcumin prevented the decrease in DK4 expression, but not in cyclin D1. These results demonstrate that ERKs and JNKs are responsible for the decrease of cyclin D1 and CDK4 expression levels in HELF induced by silica. Activator protein‐1 (AP‐1) was responsible for the decrease of CDK4 expression level, but not that of cyclin D1. The findings help to explain the mechanisms of diseases induced by silica.
Developmental cardiac electrophysiology recent advances in cellular physiology
Authors: Wetzel Glenn T. , Klitzner Thomas S. 
Published: July 2008

Abstract
This overview of cardiac ion channel development does not suggest any particular theme underlying the expression or regulation of all channel subtypes. Calcium and potassium channels generally exhibit increased expression in more mature hearts. However, this increase in channel number or activity as determined under voltage clamp conditions may not be translated into increased activity in vivo. Concomitant changes in other physiological factors such as local intracellular Ca2+ accumulation, increased resting membrane potential and decreased heart rate in mature heart may inhibit or augment channel activity. Na(+)-Ca2+ exchange activity appears to decrease with development, possibly reflecting its decreasing role in both systolic and diastolic Ca2+ regulation. Na+ channel activity follows a middle course, exhibiting little change in channel conductance. The reported shift in the voltage dependence of channel inactivation toward more negative membrane potentials may reflect a concomitant shift in the resting membrane potential in mature heart. However, this change is in the direction opposite to that reported for L-type Ca2+ channel inactivation, suggesting that the regulation of these channels is not modulated by a common factor such as membrane surface charge. A detailed characterization of multiple channel subtypes in mature myocardium has resulted in significant advances in models of the cardiac action potential and excitation-contraction coupling. Recently, developmental changes in ion channel physiology have been described, setting the stage for a comparable elucidation of the ontogeny of the cardiac action potential. Ca2+ and K+ channel currents generally become more prominent with development. In contrast, developmental changes in Na+ currents are less dramatic and Na(+)-Ca2+ exchange currents appear to decrease with age. These changes may, in part, be reflected by the increasingly important role of transsarcolemmal Ca2+ influx in triggering Ca2+ release from the SR in mature heart as compared to its direct role of providing Ca2+ for cell contraction in immature heart. These developmental changes in ion channel expression and function are likely to have a significant effect on the generation of the action potential in individual myocytes. Developmental changes in the characteristics of the action potential may then have a major influence on the initiation, propagation and termination of autonomic, triggered, and re-entrant arrhythmias. Progress in this area provides an essential foundation for the evolution of a systematic approach to pediatric arrhythmias comparable to that under development for mature heart [3]
GREEN'S FUNCTIONS AND REGULARIZED TRACES OF STURM–LIOUVILLE OPERATORS ON GRAPHS
Authors: Currie Sonja , Watson Bruce A. 
Published: July 2008

AbstractAsymptotic approximations to the Green's functions of Sturm–Liouville boundary-value problems on graphs are obtained. These approximations are used to study the regularized traces of the differential operators associated with these boundary-value problems. Various inverse spectral problems for Sturm–Liouville boundary-value problems on graphs resembling those considered in Halberg and Kramer's ‘A generalization of the trace concept' (Duke Mathematics Journal27 (1960), 607–617), for Sturm–Liouville problems, and Pielichowski's ‘An inverse spectral problem for linear elliptic differential operators' (Universitatis Iagellonicae Acta Mathematica27 (1988), 239–246), for elliptic boundary-value problems, are solved.
PROPERTIES OF THE MAXIMAL OPERATORS ASSOCIATED WITH BASES OF RECTANGLES IN $\mathbb{R}^3$
Authors: Stokolos Alexander 
Published: July 2008

AbstractThis paper is an attempt to understand a phenomenon of maximal operators associated with bases of three-dimensional rectangles of dimensions $(t,1/t,s)$ within a framework of more general Soria bases. The Jessen–Marcinkiewicz–Zygmund Theorem implies that the maximal operator associated with a Soria basis continuously maps $L\log^2L$ into $L^{1,\infty}$. We give a simple geometric condition that guarantees that the $L\log^2L$ class cannot be enlarged. The proof develops the author's methods applied previously in the two-dimensional case and is related to theorems of Córdoba, Soria and Fefferman and Pipher.