bluuebunny/crossref_metadata_2025 huggingface dataset:
Catalytic Asymmetric Epoxidation of α,β‐Unsaturated Phosphane Oxides with a Y(O‐iPr)3/Biphenyldiol Complex
Authors: Hara Keiichi , Park So‐Young , Yamagiwa Noriyuki , Matsunaga Shigeki , Shibasaki Masakatsu
Published: May 2008

A rare‐earth‐metal‐catalyzed asymmetric epoxidation of α,β‐unsaturated phosphane oxides is described. The appropriate selection of a chiral ligand and an achiral additive is important for achieving good reactivity and enantioselectivity. A Y(O‐iPr)3/biphenyldiol complex with an achiral phosphane oxide additive afforded β‐aryl α,β‐epoxy phosphane oxides in 77–99 % yield and with 96–98 % ee. With β‐alkyl substrates, the reaction proceeded smoothly in the absence of an achiral additive, and β‐alkyl α,β‐epoxy phosphane oxides were obtained in 94–99 % yield and with 87–95 % ee.
Gestaltung, Validierung und Optimierung von Messprogrammen für geotechnische Aufgabenstellungen
Authors: Schanz Tom , Meier Jörg
Published: May 2008

Beim Entwurf von baubegleitenden Messprogrammen steht die Frage “Wo messe ich welche Größen wie häufig und mit welcher notwendigen Präzision?” im Mittelpunkt. Messprogramme sind kein Selbstzweck zur Anhäufung beliebig detaillierter und umfangreicher Daten, sondern dienen u.a. der quantitativen Beantwortung von Fragen nach der Gebrauchstauglichkeit und der Standsicherheit. Daraus leitet sich unmittelbar ein wesentlicher Abstimmungsbedarf zwischen den Verantwortlichen für die Gestaltung des Messprogramms und für die Durchführung der notwendigen Nachweise, und das im Vorfeld der eigentlichen Berechnungen, ab.

Oben gestellte Frage kann erfolgreich mit den Methoden der angewandten Mathematik beantwortet werden. Zu quantifizieren ist dazu letztendlich die Sensitivität der Systemantwort (z. B. von Deformationen, Spannungen oder hydraulischen Potentialen) bezüglich häufig zunächst unbekannter Systemparameter, wie z. B. von Anfangs‐ und Randbedingungen, Geometrien oder Materialkennwerten.

Eine umfassende messtechnische Instrumentierung ist heutzutage integraler Bestandteil der Mehrzahl aller “bedeutungsvollen” geotechnischen Projekte. Nicht zuletzt aufgrund immer anspruchsvollerer Vorhaben erweitert sich das Nutzungsgebiet der so gewonnenen Messdaten zunehmend von einer reinen Überwachung und Beweissicherung zu einem wichtigen Indikator für die Entscheidungsfindung im Rahmen der operativen Ausführung (im Sinne der “Beobachtungsmethode”). Um diese Nutzungsbereiche zu eröffnen, müssen die von Projekt zu Projekt unterschiedlich zu betrachtenden relevanten Aspekte der Systemantwort des jeweiligen Vorhabens in ausreichender Qualität und Umfang wiedergegeben werden. So ist grundsätzlich ein Messprogramm anzustreben, welches möglichst kosteneffizient ausreichende Daten zur Verfügung stellt.

Da die Planung und Definition eines solchen Messprogramms i. d. R. bereits vor Beginn der eigentlichen Bauarbeiten abgeschlossen sein muss, ist dieser Arbeitsschritt als nicht‐trivial anzusehen. Als Lösungsweg bietet sich eine numerische Modellierung des Projektes an, wobei sowohl die geplanten Arbeitsschritte als auch verschiedene messtechnische Instrumentierungen an diesem Modell numerisch untersucht werden können. In diesem Beitrag wird eine Strategie für die Analyse von Messprogrammen in Kombination mit einem objektiven Bewertungskriterium vorgeschlagen.
Molecular Characterization of the NCoA‐1–STAT 6 Interaction
Authors: Seitz Markus , Maillard Ludovic T. , Obrecht Daniel , Robinson John A.
Published: May 2008

Many protein–protein interactions involved in cell signalling, cell adhesion and regulation of transcription are mediated by short α‐helical recognition motifs with the sequence Leu‐Xaa‐Xaa‐Leu‐Leu (LXXLL, where Xaa is any amino acid). Originally observed in cofactors that interact with hormone‐activated nuclear receptors, LXXLL motifs are now known to occur in many transcription factors, including the STAT family, which transmit signals from activated cytokine receptors at the cell surface to target genes in the nucleus. STAT 6 becomes activated in response to IL‐4 and IL‐13, which regulate immune and anti‐inflammatory responses. Structural studies have revealed how an LXXLL motif located in 2.5 turns of an α‐helical peptide derived from STAT 6 provide contacts through the leucine side chains to the coactivator of transcription, NCoA‐1. However, since many protein–protein interactions are mediated by LXXLL motifs, it is important to understand how specificity is achieved in this and other signalling pathways. Here, we show that energetically important contacts between STAT 6 and NCoA‐1 are made in residues that flank the LXXLL motif, including the underlined residues in the sequence LLPPTEQDLTKLL. We also demonstrate how the affinity for NCoA‐1 of peptides derived from this region of STAT 6 can be significantly improved by optimising knobs‐into‐holes contacts on the surface of the protein. The results provide important new insights into the origins of binding specificity, and might be of practical value in the design of novel small‐molecule inhibitors of this important protein–protein interaction.
Using the eosin‐5‐maleimide binding test in the differential diagnosis of hereditary spherocytosis and hereditary pyropoikilocytosis
Authors: King May‐Jean , Telfer Paul , MacKinnon Heather , Langabeer Lisa , McMahon Corrina , Darbyshire Philip , Dhermy Didier
Published: May 2008

Background:

Flow cytometric analysis of eosin‐5‐maleimide (EMA)‐labeled red blood cells (RBCs) has been used as a screening test for the diagnosis of patients with hereditary spherocytosis (HS). We assessed the fluorescence profiles for patients having HS and hereditary pyropoikilocytosis (HPP) together with their red cell indices.

Methods:

Flow cytometry was used to analyze EMA‐labeled RBCs. Membrane protein defects and spectrin variants were identified by SDS‐polyacrylamide gel electrophoresis.

Results:

An overlay of single fluorescence peaks for normal individuals, and those with HS and HPP revealed a graded fluorescence intensity (normal > HS > HPP). The area under each peak defined a specific RBC subpopulation; namely, normal RBCs, spherocytes, and microspherocytes. HS RBCs having a gross reduction in band 3 or spectrin content gave fluorescence readings almost as low as those for HPP. Complex fluorescence profiles were obtained for isolated HS and HPP cases.

Conclusions:

The mean cell volume is a useful discriminator for HS and HPP. We presented evidence that a mixed RBC population could occur in some HS and HPP patients, either in a transient manner or for a long‐term period. A differential diagnostic scheme for detecting HPP and HS by flow cytometry is proposed. © 2008 Clinical Cytometry Society
Monitoring cytomegalovirus IE‐1 and pp65‐specific CD4+ and CD8+ T‐cell responses after allogeneic stem cell transplantation may identify patients at risk for recurrent CMV reactivations
Authors: Gratama Jan W. , Brooimans Rik A. , van der Holt Bronno , Sintnicolaas Kees , van Doornum Gerard , Niesters Hubertus G. , Löwenberg Bob , Cornelissen Jan J.
Published: May 2008

We studied the recovery of CMV‐specific CD4+ and CD8+ T‐cell immunity in 52 recipients of allogeneic stem cell transplantation (SCT). The proportions of IFN‐γ‐producing CD4+ and CD8+ T cells upon in vitro activation using peptide pools representing the CMV pp65 and IE‐1 proteins were assessed at multiple time points post SCT, and correlated with the occurrence of CMV reactivation. In a retrospective analysis, recurrent CMV reactivations occurred in 9 patients and were associated with low pp65‐specific CD4+ T‐cell and low IE‐1‐specific CD8+ T‐cell reactivities, whereas patients without detectable CMV reactivation (n = 30) or a single reactivation (n = 13) showed a better recovery of these immune responses. CD4+ T‐cell responses to IE‐1 were infrequent in most patients, whereas CD8+ T‐cell responses to pp65 occurred frequently, but did not correlate with protection against (recurrent) reactivation. Prospectively, CMV‐specific T‐cell responses could be studied prior to 14 reactivation episodes in 8 patients. CD4+ T‐cell responses to IE‐1 and pp65 were positive in only 1 and 2 episodes, respectively. CD8+ T‐cell responses against IE‐1 were positive in 4, but against pp65 in 12 episodes, again showing that CD8+ T‐cell reactivity against pp65 did not prevent CMV reactivation. Thus, monitoring of particular CMV‐specific CD4+ and CD8+ T‐cell responses after allogeneic SCT may identify patients at risk for recurrent CMV reactivations. © 2008 Clinical Cytometry Society
Vascular disease and diabetes: is hypoglycaemia an aggravating factor?
Authors: Wright Rohana J. , Frier Brian M.
Published: May 2008

Acute hypoglycaemia provokes profound physiological changes affecting the cardiovascular system and several haematological parameters, principally as a consequence of sympatho‐adrenal activation and counter‐regulatory hormonal secretion. Many of these responses have an important role in protecting the brain from neuroglycopenia, through altering regional blood flow and promoting metabolic changes that will restore blood glucose to normal. In healthy young adults the cardiovascular effects are transient and have no obvious detrimental consequences. However, some of the effected changes are potentially pathophysiological and in people with diabetes who have developed endothelial dysfunction, they may have an adverse impact on a vasculature that is already damaged. The acute haemodynamic and haematological changes may increase the risk of localized tissue ischaemia, and major vascular events can certainly be precipitated by acute hypoglycaemia. These include myocardial and cerebral ischaemia and occasionally infarction. Established diabetic retinopathy often deteriorates after strict glycaemic control is instituted, the latter being associated with a threefold increase in frequency of severe hypoglycaemia, and enhanced exposure to mild hypoglycaemia. The possible mechanisms underlying these hypoglycaemia‐induced effects include haemorrheological changes, white cell activation, vasoconstriction, and the release of inflammatory mediators and cytokines. The concept that acute hypoglycaemia could aggravate vascular complications associated with diabetes is discussed in relation to evolving comprehension of the pathogenesis of atherosclerosis and blood vessel disease. Copyright © 2008 John Wiley & Sons, Ltd.
Synthesis of functionalized 1‐trimethylsiloxy‐substituted O‐trimethylsilyl alkylphosphonites and their derivatives
Authors: Prishchenko Andrey A. , Livantsov Mikhail V. , Novikova Olga P. , Livantsova Ludmila I. , Petrosyan Valery S.
Published: May 2008

Nucleophilic addition of trimethylsilyl esters of tricoordinate organophosphorus acids to various functionalized aldehydes with vinyl, aryl, and heterocyclic fragments is proposed as a convenient method for the synthesis of new 1‐trimethylsiloxysubstituted alkylphosphonites and their derivatives at mild conditions. Also the new functionalized derivatives of these phosphonites, including amino groups as well as certain properties of these compounds as important precursors of new functionalized 1‐hydroxyalkylorganophosphorus acids, are presented. © 2008 Wiley Periodicals, Inc. Heteroatom Chem 19:352–359, 2008; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/hc.20430
Nucleophilic catalysis of phosphorus trichloride oxygen oxidation
Authors: Bezgubenko Ludmila V. , Pipko Sergey E. , Shalimov Alexandr A. , Sinitsa Anatoliy D.
Published: May 2008

The effect of nucleophilic catalysis on phosphorus trichloride oxygen oxidation is discovered. A number of nucleophilic catalysts for the phosphorus trichloride oxidation are found. Triethylamine, 4‐dimethylaminopyridine (DMAP), and tetramethylurea are amongst them. © 2008 Wiley Periodicals, Inc. Heteroatom Chem 19:408–411, 2008; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/hc.20439
Reactions of tris(dimethylsilyl)methane and polymers containing si—h groups with various hydroxy compounds under aerobic and mild conditions
Authors: Safa Kazem D. , Tofangdarzadeh Shahin , Ayenadeh Hossein Heydari
Published: May 2008

Tris(dimethylsilyl)methane, (HMe2Si)CH, reacts with n‐propyl, iso‐propyl, n‐butyl, s‐butyl, iso‐butyl, n‐pentyl, s‐pentyl, n‐hexyl alcohol, and phenol in the presence of chloroplatinic acid (H2PtCl6ċ6H2O) in air to give products (ROMe2Si)3CH (where R is n‐propyl, iso‐propyl, n‐butyl, s‐butyl, iso‐butyl, n‐pentyl, s‐pentyl, n‐hexyl, phenyl). Similar reactions with benzyl alcohol and acetic acid lead to the unexpected products, (PhCH2)2O and HC(Me2SiOSiMe2)3CH, respectively. The compound (n‐BuOMe2Si)3CSiMe2H was made from (n‐BuOMe2Si)3CH by treatment with lithium diisopropylamide, followed by quenching with HMe2SiCl. The homopolymer poly{(4‐chloromethyl)styrene} and copolymers with styrene (in 1:1 and 1:3 mol ratio) were synthesized by free radical polymerization, and (HMe2Si)3C groups were linked to them by nucleophilic substitution reactions between (HMe2Si)3CLi and the chloromethyl groups of the polymer side chains. The resulting functional polymers containing Si—H bonds reacted with various alcohols in the presence of chloroplatinic acid under heterogeneous conditions. © 2008 Wiley Periodicals, Inc. Heteroatom Chem 19:365–376, 2008; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/hc.20440
Silica‐supported ICl as a novel heterogeneous system for the rapid oxidation of urazoles to triazolinediones
Authors: Karami Bahador , Mallakpour Shadpour , Farahi Mahnaz
Published: May 2008

ICl–SiO2 as a new reactive system was prepared by the treatment of iodine monochloride with an activated silica gel in chloroform. ICl–SiO2 in a heterogeneous system efficiently oxidized urazoles to the corresponding triazolinediones under mild conditions in high yields at room temperature. © 2008 Wiley Periodicals, Inc. Heteroatom Chem 19:389–393, 2008; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/hc.20444
Phosphorylated VEGFR2/KDR receptors are widely expressed in B‐cell non‐Hodgkin's lymphomas and correlate with hypoxia inducible factor activation
Authors: Giatromanolaki Alexandra , Koukourakis Michael I. , Pezzella Francesco , Sivridis Efthimios , Turley Helen , Harris Adrian L. , Gatter Kevin C.
Published: May 2008

The expression of hypoxia inducible factors (HIF) 1α and 2α, of vascular endothelial growth factor (VEGF) and of the phosphorylated form of its receptor VEGFR2 (pVEGFR2/KDR) were investigated immunohistochemically in a series of 146 B‐cell non‐Hodgkin's lymphomas and 48 normal lymph nodes. These proteins were significantly up‐regulated in neoplastic lymphocytes and a significantly higher expression of HIF1α (p = 0.05), VEGF (p = 0.02) and pVEGFR2/KDR (p = 0.007) was recorded in diffuse large B‐cell lymphomas(DLBCL) compared to follicular lymphomas (FL). A strong statistical association of pVEGFR2/KDR expression with high HIF1α, HIF2α and VEGF was noted in both DLBCL and FL. HIF1α andHIF2α were linked with VEGF expression but no association between HIF1α and HIF2α was noted. Vascular density was significantly higher in the lymphoma compared to normal tissue, but there was no association with any of the examined parameters. It is concluded that the VEGF/receptor pathway is active in more than half of NHLs and particularly in DLBCL. The intimate correlation of VEGF production with the presence of phosphorylated VEGF‐receptors strongly supports the concept of an autocrine pathway. The strong association of HIFαs with the expression of VEGF and pVEGFR2/KDR found in the study provide strong evidence on the role of HIFαs inthe activation of angiogenic and VEGF‐autocrine pathways that may be critical therapeutic targets for HIF‐inhibitors or other anti‐angiogenic agents. Copyright © 2008 John Wiley & Sons, Ltd.
Model data selection using gamma test for daily solar radiation estimation
Authors: Remesan R. , Shamim M. A. , Han D.
Published: May 2008

Hydrological modelling is a complicated procedure and there are many tough questions facing all modellers: what input data should be used? how much data is required? and what model should be used? In this paper, the gamma test (GT) has been used for the first time in modelling one of the key hydrological components: solar radiation. The study aimed to resolve the questions about the relative importance of input variables and to determine the optimum number of data points required to construct a reliable smooth model. The proposed methodology has been studied through the estimation of daily solar radiation in the Brue Catchment, the UK. The relationship between input and output in the meteorological data sets was achieved through error variance estimation before the modelling using the GT. This work has demonstrated how the GT helps model development in nonlinear modelling techniques such as local linear regression (LLR) and artificial neural networks (ANN). It was found that the GT provided very useful information for input data selection and subsequent model development. The study has wider implications for various hydrological modelling practices and suggests further exploration of this technique for improving informed data and model selection, which has been a difficult field in hydrology in past decades. Copyright © 2008 John Wiley & Sons, Ltd.
Effects of subsurface drainage tiles on streamflow in Iowa agricultural watersheds: Exploratory hydrograph analysis
Authors: Schilling Keith E. , Helmers Matthew
Published: May 2008

Flow from artificial subsurface (tile) drainage systems may be contributing to increasing baseflow in Midwestern rivers and increased losses of nitrate‐nitrogen. Standard hydrograph analysis techniques were applied to model simulation output and field monitoring from tile‐drained landscapes to explore how flow from drainage tiles affects stream baseflow and streamflow recession characteristics. DRAINMOD was used to simulate hydrologic response from drained (24 m tile spacing) and undrained agricultural systems. Hydrograph analysis was conducted using programs PART and RECESS. Field monitoring data were obtained from several monitoring sites in Iowa typical of heavily drained and less‐drained regions. Results indicate that flow from tile drainage primarily affects the baseflow portion of a hydrograph, increasing annual baseflow in streams with seasonal increases primarily occurring in the late spring and early summer months. Master recession curves from tile‐drained watersheds appear to be more linear than less‐tiled watersheds although comparative results of the recession index k were inconsistent. Considering the magnitude of non‐point source pollutant loads coming from tile‐drained landscapes, it is critical that more in‐depth research and analysis be done to assess the effects of tile drainage on watershed hydrology if water quality solutions are to be properly evaluated. Copyright © 2008 John Wiley & Sons, Ltd.
Estrogen receptor β deficiency enhances small intestinal tumorigenesis in ApcMin/+ mice
Authors: Giroux Véronique , Lemay Frédéric , Bernatchez Gérald , Robitaille Yolaine , Carrier Julie C.
Published: May 2008

Clinical evidence suggests that estradiol replacement therapy reduces colon cancer risk in ‘post’menopausal women. In colon epithelial cells, the estrogen receptor β (ERβ) is the predominant ER subtype and is thought to mediate the genomic effect of estrogens. The first aim of this study was to investigate the consequence of ERβ deficiency on intestinal tumorigenesis in the ApcMin/+ mouse model. Furthermore, to explore the biological mechanisms by which estrogens may influence the pathogenesis of colorectal cancer, we performed gene expression profiles in colonocytes from ovariectomized wild‐type (WT) vs. ERβ−/− mice, treated with estradiol (E2) or vehicle. Specifically in female, ERβ deficiency was found to be associated with higher adenoma multiplicity in the small intestine, but not in the colon. Furthermore, tumors from ERβ−/−ApcMin/+ female mice were on average significantly larger than those from control ApcMin/+ mice. Higher steady‐state proliferation in epithelial cells of the jejunum and colon from ERβ−/−ApcMin/+ vs. ApcMin/+ female mice was confirmed by BrdU incorporation assay. Interestingly, functional categorization of microarray results revealed the TGFβ signaling pathway to be modulated in colonocytes, especially for the WT + E2 vs. WT + Vehicle and the ERβ−/− + E2 vs. WT + E2 comparisons. Using quantitative PCR analysis, we observed transcripts from ligands of the TGFβ pathway to be upregulated in colonocytes from E2‐treated WT and ERβ−/− mice and downregulated in ERβ‐deficient mice, mostly in an E2‐independent manner. Therefore, our results demonstrate that ERβ deficiency enhances small intestinal tumorigenesis and suggest that modulation of the TGFβ signaling pathway could contribute to the protective role of estrogens on intestinal tumorigenesis. © 2008 Wiley‐Liss, Inc.
Identification of pyruvate kinase type M2 as potential oncoprotein in squamous cell carcinoma of tongue through microRNA profiling
Authors: Wong Thian‐Sze , Liu Xiao‐Bing , Chung‐Wai Ho Ambrose , Po‐Wing Yuen Anthony , Wai‐Man Ng Raymond , Ignace Wei William
Published: May 2008

MicroRNAs (miRNAs) are noncoding RNAs with specific regulatory role in gene expression. Recent reports suggested their involvement in human malignancies. Currently, there is no information concerning miRNA expression and functions in squamous cell carcinoma (SCC) of tongue. In this study, we evaluated the expression patterns of 156 mature miRNAs in tongue SCC using Taqman‐based microRNA assays. Of these 156 miRNAs, miR‐133a and miR‐133b were significantly reduced in tongue SCC cells in comparison with the paired normal epithelial cells. Tongue SCC cell lines transfected with miR‐133a and miR‐133b precursors displayed reduction in proliferation rate. In addition, the number of apoptotic cells was increased in response to the introduction of precursors. Computational target gene prediction suggested that both miR‐133a and miR‐133b are targeting transcript of pyruvate kinase type M2 (PKM2), a potential oncogene in solid cancers. In tongue SCC cell lines, PKM2 expression was reduced in response to miR‐133a and miR‐133b precursors transfection. Immunohistochemical staining results of tongue SCC tissues suggested that PKM2 was overexpressed in tongue SCC and was associated with the downregulation of miR‐133a and miR‐133b. Our results suggested that aberrant reduction of miR‐133a and miR‐133b was associated with the dysregulation of PKM2 in SCC of tongue. © 2008 Wiley‐Liss, Inc.
The effect of polymer composition on the gelation behavior of PLGA‐g‐PEG biodegradable thermoreversible gels
Authors: Tarasevich B. J. , Gutowska A. , Li X. S. , Jeong B.‐M.
Published: May 2008

Graft copolymers consisting of a poly(D,L‐lactic acid‐co‐glycolic acid) backbone grafted with polyethylene glycol side chains were synthesized and formed thermoreversible gels in aqueous solutions that exhibited solution behavior at low temperature and sol‐to‐gel transitions at higher temperature. The composition of the polymer and relative amounts of polylactic acid, glycolic acid, and ethylene glycol were varied by controlling the precursor concentrations and reaction temperature. The gelation temperature could be systematically tailored from 15 to 34°C by increasing the concentration of polyethylene glycol in the graft copolymer. The gelation temperature also depended on the polymer molecular weight and concentration. This work has importance for the development of water soluble gels with tailored compositions and gelation temperatures for use in tissue engineering and as injectable depots for drug delivery. © 2008 Wiley Periodicals, Inc. J Biomed Mater Res, 2009
Osteoblast adhesion on novel machinable calcium phosphate/lanthanum phosphate composites for orthopedic applications
Authors: Ergun Celaletdin , Liu Huinan , Webster Thomas J.
Published: May 2008

Lanthanum phosphate (LaPO4, LP) was combined with either hydroxyapatite (HA) or tricalcium phosphate (TCP) to form novel composites for orthopedic applications. In this study, these composites were prepared by wet chemistry synthesis and subsequent powder mixing. These HA/LP and TCP/LP composites were characterized in terms of phase stability and microstructure evolution during sintering using X‐ray diffraction (XRD) and scanning electron microscopy (SEM). Their machinability was evaluated using a direct drilling test. For HA/LP composites, LP reacted with HA during sintering and formed a new phase, Ca8La2(PO4)6O2, as a reaction by‐product. However, TCP/LP composites showed phase stability and the formation of a weak interface between TCP and LP machinability when sintered at 1100°C, which is crucial for achieving desirable properties. Thus, these novel TCP/LP composites fulfilled the requirements for machinability, a key consideration for manufacturing orthopedic implants. Moreover, the biocompatibility of these novel LP composites was studied, for the first time, in this paper. In vitro cell culture tests demonstrated that the LP and its composites supported osteoblast (bone‐forming cell) adhesion similar to natural bioceramics (such as HA and TCP). In conclusion, these novel LP composites should be further studied and developed for more effectively treating bone related diseases or injuries. © 2008 Wiley Periodicals, Inc. J Biomed Mater Res, 2009
New injectable and radiopaque antibiotic loaded acrylic bone cements
Authors: Hernandez Lidia , Muñoz M. Eugenia , Goñi Isabel , Gurruchaga Mariló
Published: May 2008

The use of antibiotic loaded bone cements (ALBCs) has become a common clinical practice in the prevention and treatment of prosthesis‐related infections. However, due to antibiotic resistance, there is a general interest in broadening the antibacterial spectrum of currently used drugs. The aim of this work is to formulate ALBCs for specific use in vertebroplasty and kyphoplasty, and to study the effect of the addition of ciprofloxacin alone and in combination with vancomycin on some properties of the cement. The cements were formulated using bismuth salicylate as the radiopacifier. The setting properties, residual monomer content, release of antibiotics, rheological behavior, injectability, and mechanical properties of these formulations were studied. They showed long setting times and low curing temperatures. From the release studies, antibacterial properties are assumed because the concentration of released antibiotic was higher than the minimum effective. Although the experimental cements had slightly reduced mechanical properties, the other alterations shown were negligible. © 2008 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2008
A new efficient method for one‐pot conversions of aryl carboxylic acids into nitriles without solvent
Authors: Cao Yu‐Qing , Zhang Zhan , Guo Yan‐Xin
Published: May 2008

A new efficient method for synthesising nitriles, important organic reagents, is reported in this paper. In an environmentally benign solvent‐free system, aryl carboxylic acids were converted into the corresponding nitriles via one‐pot reactions, by amidation with ethyl carbamate followed by dehydration with thionyl chloride, in excellent yields. The results showed that the method has the advantages of lower cost, higher yield, less pollution and greater ease of work‐up. Copyright © 2008 Society of Chemical Industry
Ligand‐induced dimer formation of calmodulin
Authors: Zhang Yong , Tan Hongwei , Jia Zongchao , Chen Guangju
Published: May 2008

Calmodulin (CaM) can bind to numerous proteins in several interaction modes. Recently a new mode of interaction was discovered, in which two CaM molecules form an X‐shaped dimer and two binding sites to trap the CaM‐binding domain (CBD) of calcineurin subunit A. However, the X‐shaped CaM dimer alone without ligand has not been observed. We performed molecular dynamics (MD) simulations and used MM_PBSA approach to investigate the properties of this new binding mode using ligand‐bound and ‐free dimer systems. MD trajectories show that two peptides of CBD play a critical role in stabilizing the X‐shaped conformation of the CaM dimer which would otherwise be unstable, leading to dimer disassembly in the absence of the ligands. Furthermore, we have analyzed the interaction free energy of the complex by MM‐PBSA method and provide further evidence to demonstrate that the CBD peptide ligands are responsible for the stabilization of the dimer. Comparing this new binding mode with the classical one represented by CaM in complex with smooth muscle myosin light chain kinase, we conclude that this new binding mode isinduced by the CBD of calcineurin subunit A. Our results explain the fact that the X‐shaped CaM dimer structure has never been observed in the absence of ligands. Copyright © 2008 John Wiley & Sons, Ltd.
Cytomegalovirus prophylaxis with valganciclovir in cytomegalovirus‐seropositive kidney‐transplant patients
Authors: Wéclawiak Hugo , Kamar Nassim , Mengelle Catherine , Guitard Joëlle , Esposito Laure , Lavayssière Laurence , Cointault Olivier , Ribes David , Rostaing Lionel
Published: May 2008

The aims of this prospective, open‐label, single‐center pilot study were to assess the efficacy and safety of human cytomegalovirus (HCMV) prophylaxis using valganciclovir in HCMV‐ seropositive kidney‐transplant patients to prevent HCMV infection and disease. Fifty‐one HCMV seropositive kidney‐transplant patients recipients who received transplants between 1 December 2005 and 30 November 2006 were included in the study. Valganciclovir was given from transplantation up to 114 (37–329) days, and was adapted to renal function, i.e., 900 mg/d if calculated creatinine clearance was >60 ml/min, or 450 mg/day if it was <60 ml/min. HCMV DNAemia was assessed every 2 weeks during prophylaxis, and on the same basis for 3 months post‐prophylaxis. Immunosuppression was based on calcineurin inhibitors (ciclosporine A = 22; tacrolimus = 11), with mycophenolate mofetil (n = 51), and low‐dose steroids. Eighteen patients received no calcineurin‐inhibitors, but Belatacept instead. During valganciclovir prophylaxis, asymptomatic HCMV DNAemia was observed in one patient, and no case of HCMV disease occurred. Within 252 days (45–425) post‐valganciclovir prophylaxis, HCMV DNAemia was detected in 23.5% (n = 12) of patients, of whom two had two or more consecutive HCMV DNAemias. Valganciclovir prophylaxis in HCMV‐seropositive kidney‐transplant patients is effective for preventing cytomegalovirus disease. J. Med. Virol. 80: 1228–1232, 2008. © 2008 Wiley‐Liss, Inc.
Kinetics of hepatitis C viral RNA and HCV‐antigen during dialysis sessions: Evidence for differential viral load reduction on dialysis
Authors: Kaiser Thorsten , Damerow Hans C. , Tenckhoff Solveig , Finger Andrea , Böttcher Isabella , Hafer Carsten , Schwarz Anke , Lüth Johann B. , Gürtler Hans Schmidt , Colucci Giuseppe , Manns Michael P. , Wedemeyer Heiner , Tillmann Hans L.
Published: May 2008

Hepatitis C infection is a common problem in dialysis units. The prevalence ranges from 3% to more than 50%. Several reports have described a variable reduction of HCV‐RNA during hemodialysis treatment sessions. But so far nothing is known about the HCV antigenemia or the kinetics of the reduction of HCV‐RNA and HCV antigenemia during these sessions. HCV‐RNA was monitored using the VERSANT HCV bDNA assay 3.0 (Bayer Healthcare Diagnostics, Leverkusen, Germany) or the HCV‐Monitor TaqMan (Roche Diagnostics). HCV antigenemia was tested by using Ortho‐trac‐C® assay (Ortho Clinical Diagnostics, Neckargemünd, Germany). Kinetics of HCV‐RNA were available in 15 dialysis sessions measured by bDNA assay and in 5 dialysis sessions measured by rt‐PCR. Quantitative HCV‐antigenemia was available in fourteen dialysis sessions. Not only HCV‐RNA but as expected also the HCV‐antigenemia fell during the dialysis session. However, while the average reduction of HCV‐antigen appears steady and linear, the level of HCV‐RNA seems to be stable during the first 3 hr of dialysis, and decreases rapidly during the last 2 hr. The results seem to be independent of the HCV‐RNA detection method. The different kinetics of HCV RNA and HCV antigen load suggest that there are different mechanisms responsible for the reduction of the HCV antigen and HCV‐RNA, respectively. Reduction of viral load during dialysis session indicates a potential benefit of dialysis in case of HCV associated antiviral therapy. J. Med. Virol. 80: 1195–1201, 2008. © 2008 Wiley‐Liss, Inc.
Sequence analysis of the capsid gene of Aichi viruses detected from Japan, Bangladesh, Thailand, and Vietnam
Authors: Pham Ngan Thi Kim , Trinh Quang Duy , Khamrin Pattara , Nguyen Tuan Anh , Dey Shuvra Kanti , Phan Tung Gia , Hoang Le Phuc , Maneekarn Niwat , Okitsu Shoko , Mizuguchi Masashi , Ushijima Hiroshi
Published: May 2008

Sequence analysis of the capsid gene of Aichi viruses was performed on 12 strains detected in Japan, Bangladesh, Thailand, and Vietnam during 2002–2005. The phylogenetic tree constructed from 17 nucleotide sequences of the capsid gene of the strains studied and reference strains demonstrated that Aichi virus strains clustered into two branches. A classification of Aichi viruses based on the capsid gene was proposed, in which lineage I consists of the Aichi virus strains detected from Japan, Thailand, Vietnam, and Germany, and lineage II includes Bangladeshi strains and a Brazilian strain. J. Med. Virol. 80: 1222–1227, 2008. © 2008 Wiley‐Liss, Inc.
Association of RANTES −403 G/A, −28 C/G and In1.1 T/C polymorphism with HIV‐1 transmission and progression among North Indians
Authors: Rathore Anurag , Chatterjee Animesh , Sivarama P. , Yamamoto Naohiko , Singhal Pradeep K. , Dhole Tapan N.
Published: May 2008

The relationships between host immune factors and HIV‐1 disease progression are still in dispute. The RANTES SNPs exhibit distinct ethnic distribution and are associated with different effects on the course of HIV infection. Therefore, impact of RANTES gene polymorphism on HIV‐1 transmission and progression needs to be evaluated. The RANTES genotypes were identified by PCR‐RFLP method and confirmed by sequencing in HIV‐1 seronegative (HSN; n = 315), HIV‐1 exposed seronegative (HES; n = 47) and HIV‐1 seropositive (HSP; n = 196) patients classified into different clinical stages (i.e. Stages I, II, III). Fisher exact test was used for statistical analysis and Arlequin software for haplotype analysis. RANTES allele −403G, −28C and In1.1 T were the predominant allele in the subject studied. HSP group have higher frequency of RANTES In1.1 T allele compared with HSN (91.32% vs. 86.19%; P = 0.013) and HES (91.32% vs. 78.72%; P = 0.001). Higher frequency of RANTES In1.1 C allele in Stage III was observed, compared with Stage I (14.28% vs. 6.39%) and was significantly associated with high risk (P = 0.047, OR = 2.439, C.I. = 1.061–5.609). Haplotype II (ACT) was significantly higher in HSP compared with HSN (9.69% vs. 1.58%) and associated with high risk (P < 0.001, OR = 6.655, C.I. = 2.443–18.132). There were no significant differences in RANTES −403 A/G and −28 C/G genotype and allele distribution in all the groups compared. Our results implicate that RANTES In1.1 T allele and haplotype II (ACT) may be a risk factor for HIV‐1 transmission while RANTES In1.1 C allele may be risk factor for disease progression among North Indians. J. Med. Virol. 80: 1133–1141, 2008. © 2008 Wiley‐Liss, Inc.
Preliminary characterization of murine cytomegaloviruses with insertional and deletional mutations in the M34 open reading frame
Authors: Baluchova Katarina , Kirby Melissa , Ahasan Mohammad M. , Sweet Clive
Published: May 2008

A viable virus could not be recovered from a mutant murine cytomegalovirus (MCMV) BAC in which the M34 ORF had been deleted (BACΔM34). In contrast, an M34 mutant virus (RcM34), in which the M34 ORF was interrupted by transposon insertion at nt 44,827 of the Smith MCMV BAC, was attenuated in replication both in tissue culture and in SCID mice. Similarly, mutant virus Rc3′ΔM34, in which the 3′‐end was deleted from nt 44,724 to nt 45,647, produced similar replication kinetics in tissue culture to RcM34 while BAC5′ΔM34, in which the 5′‐end from nt 43,083 up to nt 44,896 was deleted, was non‐viable like BACΔM34. A transcript analysis of wt and RcM34 virus‐infected cells showed that a truncated transcript encoding a putative protein of 624 amino acids was produced by RcM34, of which the amino terminal 582 amino acids would be identical to the predicted wt 854 amino acids product. Recent, re‐annotations of the MCMV genome have identified three putative M34 overlapping ORFs (m33.1, m34.1, and m34.2) that may be interrupted in the above mutants. All three were transcribed in RcM34 virus‐infected cells confirming that the RcM34 virus phenotype was probably due to interruption of the M34 ORF. These results suggest that M34, like human CMV UL34, is an essential gene. J. Med. Virol. 80: 1233–1242, 2008. © 2008 Wiley‐Liss, Inc.
Seoul virus enhances regulatory and reduces proinflammatory responses in male Norway rats
Authors: Easterbrook Judith D. , Klein Sabra L.
Published: May 2008

Zoonotic pathogens, including hantaviruses, are maintained in the environment by causing persistent infection in the absence of disease in their reservoir hosts. Spillover of hantaviruses to humans can cause severe disease that is mediated by excessive proinflammatory responses. The mechanisms mediating hantaviral persistence in rodent reservoirs remain largely unknown. Male Norway rats were inoculated with their species‐specific hantavirus, Seoul virus (SEOV), and viral RNA, cytokine, and chemokine responses were evaluated in spleen and lung tissue. More viral RNA was detectable in the lungs than spleen, with copies of SEOV peaking 15–30 days post‐inoculation (p.i.) and persisting for 60 days p.i. In the lungs, the expression and production of proinflammatory mediators (i.e., IL‐1β, IL‐6, TNF‐α, IFN‐γ, CCL5, CCL2, CX3CL1, CXCL10, VCAM, VEGF, and NOS2) remained at or below baseline throughout SEOV infection; whereas, regulatory factors, including TGF‐β and FoxP3 were elevated. Conversely, in the spleen, proinflammatory responses were induced while regulatory responses remained unchanged during infection. To determine whether reduced proinflammatory responses mediate hantavirus persistence in the lungs, male rats were administered rIL‐1β or vehicle for 30 days during SEOV infection. SEOV persistence and shedding were not affected by IL‐1β treatment. Proinflammatory responses were elevated in rIL‐1β‐treated rats, but remained within physiological levels, suggesting that supra‐physiological concentrations may be necessary for viral clearance at the cost of causing disease. Elevated regulatory responses may suppress excessively high proinflammatory responses at a site of elevated SEOV replication to contribute to viral persistence and prevent proinflammatory‐mediated disease in reservoir hosts. J. Med. Virol. 80: 1308–1318, 2008. © 2008 Wiley‐Liss, Inc.
The presence and distribution of lubricin in the caprine intervertebral disc
Authors: Shine Kristy M. , Spector Myron
Published: May 2008

Lubricin is a large, multifunctional glycoprotein that is known to play a role as a boundary lubricant in diarthrodial joint articulation. The hypothesis of this study was that lubricin is present in the intervertebral disc in a distribution consistent with serving to facilitate interlamellar tribology. The objectives were to: (1) determine the distribution of lubricin in the normal caprine disc; and (2) investigate the synthesis of lubricin by caprine annulus fibrosus (AF) and nucleus pulposus (NP) cells in vitro, using immunohistochemical methods. Caprine lumbar intervertebral discs from five levels and four animals were studied. Positive staining revealed the presence of the lubricin in the outer AF of nearly all samples. No staining was present in the inner AF or the NP. Within the outer AF, lubricin was prominent in the layers separating lamellae and in the extracellular matrix of the lamellae. Some of the AF cells within the lubricin‐positive regions demonstrated intracellular lubricin staining, suggesting that these cells may be synthesizing the lubricin protein observed. Immunohistochemistry performed on monolayer cultures of primary AF and NP cells demonstrated intracellular lubricin staining in both cell types. Thus, lubricin is selectively present in the outer caprine intervertebral disc AF, and its distribution suggests that it may play a role in interlamellar tribology. Cells from both the annulus and nucleus were found capable of synthesizing lubricin in vitro, suggesting that these cells may be a potential source of the glycoprotein under some conditions. © 2008 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 26:1398–1406, 2008
Posterior cruciate ligament removal contributes to abnormal knee motion during posterior stabilized total knee arthroplasty
Authors: Cromie Melinda J. , Siston Robert A. , Giori Nicholas J. , Delp Scott L.
Published: May 2008

Abnormal anterior translation of the femur on the tibia has been observed in mid flexion (20–60°) following posterior stabilized total knee arthroplasty. The underlying biomechanical causes of this abnormal motion remain unknown. The purpose of this study was to isolate the effects of posterior cruciate ligament removal on knee motion after total knee arthroplasty. We posed two questions: Does removing the posterior cruciate ligament introduce abnormal anterior femoral translation? Does implanting a posterior stabilized prosthesis change the kinematics from the cruciate deficient case? Using a navigation system, we measured passive knee kinematics of ten male osteoarthritic patients during surgery after initial exposure, after removing the anterior cruciate ligament, after removing the posterior cruciate ligament, and after implanting the prosthesis. Passively flexing and extending the knee, we calculated anterior femoral translation and the flexion angle at which femoral rollback began. Removing the posterior cruciate ligament doubled anterior translation (from 5.1 ± 4.3 mm to 10.4 ± 5.1 mm) and increased the flexion angle at which femoral rollback began (from 31.2 ± 9.6° to 49.3 ± 7.3°). Implanting the prosthesis increased the amount of anterior translation (to 16.1 ± 4.4 mm), and did not change the flexion angle at which femoral rollback began. Abnormal anterior translation was observed in low and mid flexion (0–60°) after removing the posterior cruciate ligament, and normal motion was not restored by the posterior stabilized prosthesis. © 2008 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 26:1494–1499, 2008
The effect of oxygen tension on the in vitro assay of human osteoblastic connective tissue progenitor cells
Authors: Villarruel Sandra M. , Boehm Cynthia A. , Pennington Mark , Bryan Jason A. , Powell Kimerly A. , Muschler George F.
Published: May 2008

Connective tissue progenitors (CTPs) are defined as the heterogeneous set of stem and progenitor cells that reside in native tissues and are capable of proliferation and differentiation into one or more connective tissue phenotypes. CTPs play important roles in tissue formation, repair, and remodeling. Therefore, in vitro assays of CTP prevalence and biological potential have important scientific and clinical relevance. This study evaluated oxygen tension as an important variable in optimizing in vitro conditions for quantitative assays of human CTPs. Bone marrow aspirates were collected from 20 human subjects and cultured using established medium conditions at ambient oxygen tensions of 1, 5, 10, and 20%. Colony‐forming efficiency (CFE), proliferation, and colony density were assessed. CFE and proliferation were greatest at 5% O2. Traditional conditions using atmospheric oxygen tension (20% O2) reduced CFE by as much as 32%. CFE and proliferation at 1% O2 were less than 5% O2 but comparable to that seen at 20% O2, suggesting that CTPs are relatively resilient under hypoxic conditions, a fact that may be relevant to their function in wound repair and their potential use in tissue engineering applications involving transplantation into settings of moderate to severe hypoxia. These data demonstrate that optimization of quantitative assays for CTPs will require control of oxygen tension. © 2008 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 26:1390–1397, 2008
Effect of age on vascularization during fracture repair
Authors: Lu Chuanyong , Hansen Erik , Sapozhnikova Anna , Hu Diane , Miclau Theodore , Marcucio Ralph S.
Published: May 2008

Age affects fracture repair; however, the underlying mechanisms are not well understood. The goal of this study was to assess the effects that age has on vascularization during fracture healing. Tibial fractures were created in juvenile (4‐week‐old), middle‐aged (6‐month‐old), and elderly (18‐month‐old) mice. The length density and surface density of blood vessels within fracture calluses were analyzed using stereology at 7 days after fracture. The expression of molecules that regulate vascular invasion of the fracture callus was also compared among the three age groups by immunohistochemistry and in situ hybridization. At 7 days after fracture, juvenile mice had a higher surface density of blood vessels compared to the middle‐aged and elderly. Hypoxia‐inducible factor‐1α protein and transcripts of vascular endothelial growth factor were detected at 3 days postinjury in juvenile but not middle‐aged and elderly mice. Stronger Mmp‐9 and ‐13 expression was detected in fracture calluses at day 7 in the juvenile compared to the middle‐aged and elderly mice. At 21 days postfracture, expression of both Mmps was more robust in the elderly than juvenile and middle‐aged animals. These data indicate that age affects vascularization during fracture repair, and the changes we observed are directly correlated with altered expression of biochemical factors that regulate the process of angiogenesis. However, whether the increased vascularization is the cause or result of accelerated bone repair in juvenile animals remains unknown. Nonetheless, our results indicate that enhancing vascularization during fracture repair in the elderly may provide unique therapeutic opportunities. © 2008 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 26:1384–1389, 2008
Chemotaxis of human articular chondrocytes and mesenchymal stem cells
Authors: Mishima Yasunori , Lotz Martin
Published: May 2008

Migration of chondrocytes and mesenchymal stem cells (MSCs) may be important in cartilage development, tissue response to injury, and in tissue engineering. This study analyzed growth factors and cytokines for their ability to induce migration of human articular chondrocytes and bone marrow‐derived mesenchymal stem cells in Boyden chamber assays.In human articular chondrocytes serum induced dose‐ and time‐dependent increases in cell migration. Among a series of growth factors and cytokines tested only PDGF induced a significant increase in cell migration. The PDGF isoforms AB and BB were more potent than AA. There was an aging‐related decline in the ability of chondrocytes to migrate in response to serum and PDGF. Human bone marrow MSC showed significant chemotaxis responses to several factors, including FBS, PDGF, VEGF, IGF‐1, IL‐8, BMP‐4, and BMP‐7. In summary, these results demonstrate that directed cell migration is inducible in human articular chondrocytes and MSC. PDGF is the most potent factor analyzed, and may be useful to promote tissue integration during cartilage repair or tissue engineering. © 2008 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 26:1407–1412, 2008