bluuebunny/crossref_metadata_2025 huggingface dataset:
A critical review of clinical trials for low‐molecular‐weight heparin therapy in unstable coronary artery disease
Authors: Husted Steen , Becker Richard , Kher Andre
Published: February 2009

Unstable angina and non‐ST‐segment elevation myocardial infarction (MI) are collectively referred to as unstable coronary artery disease (UCAD). They are conditions that share a common pathophysiology and represent frequently encountered, potentially life‐threatening clinical manifestations of advanced atherosclerosis. Therefore, treatment of UCAD is a major focus for practicing clinicians, and although pharmacologic agents have been developed that impact on patient outcome, recent data suggest that a further reduction in ischemic complications is possible. Acute‐phase treatment with aspirin is associated with a significant reduction in death and nonfatal MI in patients with UCAD. This benefit is enhanced by the addition of unfractionated heparin (UFH) to the treatment strategy; however, UFH requires careful monitoring and titration. in contrast, low‐molecular‐weight heparins (LMWHs), produced by chemical or enzymatic depolymerization of UFH, yield a predictable and consistent pharmacokinetic profile and anticoagulant response, making them an attractive treatment alternative to UFH in patients with UCAD. The optimal duration of treatment with LMWH is an important question influenced by the observation that reactivation of coagulation occurs following the early and abrupt discontinuation of heparin treatment. Early trials, such as FRISC and FRIC, demonstrated the benefit of acute therapy with dalteparin sodium; however, the results of extended treatment with dalteparin were inconclusive. The extended phase of these studies included relatively low‐risk patients, and a once‐daily, relatively low‐dose strategy was employed. The findings derived from the FRISC II trial, which used a twice‐daily dose of dalteparin, suggest a benefit for at least 60 days with extended treatment in high‐risk patients with UCAD. Although an early‐invasive treatment strategy is particularly beneficial, patients in whom early revascularization is not possible should be considered for extended treatment with dalteparin for up to 45 days, especially those awaiting percutaneous coronary intervention. Extended treatment with dalteparin therefore provides a protective “bridge” to enhance the outcome of patients with UCAD awaiting revascularization.
N‐Acetylcysteine improves microcirculatory flow during smoking: New effects of an old drug with possible benefits for smokers
Authors: Lu Qing , Björkhem Ingemar , Xiu R.‐J. , Henrksson Peter , Freyschuss Anna
Published: February 2009

Background: Cigarette smoking provokes marked acute changes in the microcirculatory vasculature, including a reduced blood flow velocity. in accordance with the hypothesis that the reduced blood flow is due to an imbalance between pro‐oxidants and oxidants, we recently showed that most of the reduction could be reversed by a high dose of vitamin C.

Hypothesis: in the present work we tested the hypothesis that N‐acetylcysteine, a mucolyticum and an antioxidant, may have an effect on the smoking‐induced changes observed by vital capillary microscopy of the nailfold.

Methods: in all, 37 healthy volunteers of both genders and with varied smoking habits were treated with N‐acetylcysteine 200 mg t.i.d. for 2 weeks. in vivo investigation of the microcirculation by capillaroscopy was performed before and after treatment.

Results: Treatment with N‐acetylcysteine significantly reduced the smoking‐induced relative decrease in capillary blood flow velocity in a group of volunteers with varied smoking habits (p=0.0016). The preventive effect was clearly significant in smokers (p=0.003).

Conclusion: Treatment with N‐acetylcysteine has a positive impact on microcirculatory flow during smoking, particularly in habitual smokers.
Inducible ventricular arrhythmias and patency of infarct‐related artery in survivors of acute myocardial infarction
Authors: Paganelli Franck , Barnay Pierre , Franceschi Frédéric , Yapo Florence , Geélaisse Richard , Lévy Samuel
Published: February 2009

Background: Patency of infarct‐related artery in patients who suffered an acute myocardial infarction (AMI) has been shown to be associated with improved survival. Ventricular tachyarrhythmias induced by programmed electrical stimulation may be predictive of arrhythmic events and sudden death.

Hypothesis: The study was undertaken to assess the possible effect of a patent infarct‐related coronary artery on induced ventricular tachyarrhythmias during programmed ventricular stimulation in survivors of AMI.

Methods: In this prospective study, programmed electrical stimulation was performed before hospital discharge (14 ± 2 days) in 79 patients who survived an AMI. Patients were subdivided into two groups: Group 1 with patent infarct‐related coronary artery (n = 64) and Group 2 with occluded infarct‐related artery (n = 15) at coronary angiography performed at 14 ± 2 days. These two groups were comparable in terms of mean left ventricular ejection fraction, location of infarct‐related artery, number of diseased vessels, peak creatine kinase value, and infarct location.

Results: Ventricular arrhythmias were induced in 21 patients (32.6%) of Group 1 and 4 patients (26.6%) of Group 2. This difference was not statistically significant.

Conclusion: This study suggests that ventricular arrhythmias induced by programmed ventricular stimulation in survivors of AMI did not differ whether the infarct‐related artery was patent or occluded. Other factors may play a role in electrical instability as assessed by programmed ventricular stimulation.
Usefulness of lavage cytology during endoscopic transpapillary catheterization into the gallbladder in the cytological diagnosis of gallbladder disease
Authors: Naito Yoshiki , Okabe Yoshinobu , Kawahara Akihiko , Taira Tomoki , Isida Yusuke , Kaji Ryouhei , Sata Michio , Ureshino Hiroki , Mikagi Kazuhiro , Kinoshita Hisafumi , Yasumoto Makiko , Kusano Hironori , Kage Masayoshi , Yano Hirohisa
Published: February 2009

Many studies have reported methods of cell collection involving percutaneous transhepatic cholangiodrainage (PTCD) and fine‐needle aspiration cytology for the diagnosis of gallbladder disease. However, few studies have described the use of a transpapillary approach, i.e., endoscopic transpapillary catheterization into the gallbladder (ETCG). In this study, we analyzed cells collected by ETCG to evaluate its usefulness in the cytological diagnosis of gallbladder disease.

The subjects were 19 patients who had undergone ETCG for the diagnosis of gallbladder disease. Of these patients, 11 and 8 had gallbladder cancer and benign gallbladder disease, respectively. We also evaluated the diagnostic accuracy of PTCD cytology performed in 15 patients with gallbladder cancer.

Specimens were cytologically diagnosed as normal or benign, indeterminate, suspected malignancy, malignant, and inadequate in 47% (9/19), 11% (2/19), 0% (0/19), 37% (7/19), and 5% (1/19) of patients, respectively. Specimens were diagnosed as malignant, indeterminate, normal or benign, and inadequate in 7, 2, 1, and 1, respectively, of the 11 patients diagnosed with gallbladder cancer. The sensitivity and specificity of ETCG cytology were 78 and 100%, respectively, whereas the diagnostic accuracy of PTCD cytology was 20% (3/15). None of the patients developed complications of ETCG.

Despite its technical difficulty, ETCG for bile cytology allows the collection of adequate cell numbers from patients with benign disease or gallbladder cancer and facilitates a cytological diagnosis, making it a useful method for collecting cells. Diagn. Cytopathol. 2009. © 2009 Wiley‐Liss, Inc.
Acheate‐scute like 1 (Ascl1) is required for normal delta‐like (Dll) gene expression and notch signaling during retinal development
Authors: Nelson Branden R. , Hartman Byron H. , Ray Catherine A. , Hayashi Toshinori , Bermingham‐McDonogh Olivia , Reh Thomas A.
Published: February 2009

Delta gene expression in Drosophila is regulated by proneural basic helix–loop–helix (bHLH) transcription factors, such as acheate‐scute. In vertebrates, multiple Delta‐like and proneural bHLH genes are expressed during neurogenesis, especially in the retina. We recently uncovered a relationship between Acheate‐scute like 1 (Ascl1), Delta‐like genes, and Notch in chick retinal progenitors. Here, we report that mammalian retinal progenitors are also the primary source of Delta‐like genes, likely signaling through Notch among themselves, while differentiating neurons expressed Jagged2. Ascl1 is coexpressed in Delta‐like and Notch active progenitors, and required for normal Delta‐like gene expression and Notch signaling. We also reveal a role for Ascl1 in the regulation of Hes6, a proneurogenic factor that inhibits Notch signaling to promote neural rather than glial differentiation. Thus, these results suggest a molecular mechanism whereby attenuated Notch levels coupled with reduced proneurogenic activity in progenitors leads to increased gliogenesis and decreased neurogenesis in the Ascl1‐deficient retina. Developmental Dynamics 238:2163–2178, 2009. © 2009 Wiley‐Liss, Inc.
c‐fos elimination compensates for disabled‐2 requirement in mouse extraembryonic endoderm development
Authors: Yang Dong‐Hua , Smith Elizabeth R. , Cai Kathy Qi , Xu Xiang‐Xi
Published: February 2009

Disabled‐2 (Dab2) is expressed in primitive endoderm cells as they are differentiating from the inner cell mass and dab2 deficiency in mice results in lethality at E5.5–E6.5 due to the disorganization of the endoderm layers. Here we show that Dab2 suppresses c‐Fos expression in endoderm cells. A morphological normal primitive endoderm layer was observed in putative E5.5 dab2 (−/−):c‐fos (−/−) embryos, indicating that the primitive endoderm defect due to the loss of Dab2 is rescued by deletion of the c‐fos gene. The lethality of the double knockout embryos was delayed until E9.5–E10.5 and the defective embryos failed to undergo organogenesis. We conclude that Dab2 plays a role in epithelial organization by suppression of c‐Fos expression and suggest that unsuppressed c‐Fos can lead to disruption of primitive endoderm epithelial organization, yet an additional dab2 function is required for later organogenesis. Developmental Dynamics 238:514–523, 2009. © 2009 Wiley‐Liss, Inc.
Identification of embryonic pancreatic genes using Xenopus DNA microarrays
Authors: Hayata Tadayoshi , Blitz Ira L. , Iwata Nahoko , Cho Ken W.Y.
Published: February 2009

The pancreas is both an exocrine and endocrine endodermal organ involved in digestion and glucose homeostasis. During embryogenesis, the anlagen of the pancreas arise from dorsal and ventral evaginations of the foregut that later fuse to form a single organ. To better understand the molecular genetics of early pancreas development, we sought to isolate markers that are uniquely expressed in this tissue. Microarray analysis was performed comparing dissected pancreatic buds, liver buds, and the stomach region of tadpole stage Xenopus embryos. A total of 912 genes were found to be differentially expressed between these organs during early stages of organogenesis. K‐means clustering analysis predicted 120 of these genes to be specifically enriched in the pancreas. Of these, we report on the novel expression patterns of 24 genes. Our analyses implicate the involvement of previously unsuspected signaling pathways during early pancreas development. Developmental Dynamics 238:1455–1466, 2009. © 2009 Wiley‐Liss, Inc.
A study of uniform approximation of equivalent permittivity for index‐modulated gratings
Authors: Sugano Shota , Wakabayashi Hideaki , Inai Hiroshi
Published: February 2009

It is well known that surface‐relief dielectric gratings with rectangular profile can be treated by uniform approximation of the equivalent permittivity when the periodicity is very small compared with the wavelength. In optics, this phenomenon is the equivalent anisotropic effects or the form birefringence. When the periodicity is very small, the equivalent anisotropic effects will be shown in index‐modulated gratings. In this paper, the uniform approximation is described for the electromagnetic scattering problem of index‐modulated gratings. The scattering properties of dielectric slabs are calculated by transmission‐line theory and the equivalent permittivity obtained from our proposed formulation of the uniform approximation. Scattering by index‐modulated gratings is analyzed rigorously by matrix eigenvalue calculations using the Fourier expansion method and spatial harmonics expansions. When the periodicity is very small, the results are in good agreement. By investigating the difference between the equivalent permittivity and the numerical values corresponding to the permittivity of the index‐modulated gratings, the conditions of applicability of the uniform approximation are shown. The equivalent anisotropic effects of various profiles are compared. © 2009 Wiley Periodicals, Inc. Electron Comm Jpn, 91(11): 28–36, 2008; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/ecj.10181
Active coordinated operation of a distribution network system for many connections of distributed generators
Authors: Hayashi Yasuhiro , Kawasaki Shoji , Matsuki Junya , Wakao Shinji , Baba Junpei , Hojo Masahide , Yokoyama Akihiko , Kobayashi Naoki , Hirai Takao , Oishi Kohei
Published: February 2009

Recently, the total number of distributed generators (DGs) such as photovoltaic generation system and wind turbine generation system connected to an actual distribution network has increased drastically. The distribution network connected to many distributed generators must be operated keeping reliability of power supply, power quality, and loss minimization. In order to accomplish active distribution network operation to take advantage of many connections of DGs, a new coordinated operation of distribution system with many connections of DGs is necessary. In this paper, the authors propose a coordinated operation of distribution network system connected to many DGs by using newly proposed sectionalizing switch control, sending voltage control, and computation of available DG connection capability. In order to check the validity of the proposed coordinated operation of distribution system, numerical simulations using the proposed coordinated distribution system operation are carried out in a practical distribution network model. © 2009 Wiley Periodicals, Inc. Electr Eng Jpn, 167(3): 46–57, 2009; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/eej.20655
A fault location method using air‐gap fluxes of synchronous generator
Authors: Matsuki Junya , Hayashi Yasuhiro , Nakano Toshikazu , Funasaki Yoichi
Published: February 2009

This paper deals with an experimental investigation of a novel fault location method using air‐gap flux distributions of a synchronous generator connected to a power system. Air‐gap fluxes are the sum of field fluxes and armature reaction fluxes. Changes in armature current and field current at a fault contribute directly to the armature reaction fluxes and field fluxes, then resultant air‐gap fluxes. Therefore, air‐gap fluxes can be utilized to locate a fault. Wavelet analysis is applied to the induced voltages of search coils, which are wound around a stator tooth top for measurement of the air‐gap flux. It is shown that the fault type and location can be estimated based on the change in the search coil voltages measured during the fault. © 2009 Wiley Periodicals, Inc. Electr Eng Jpn, 167(3): 20–27, 2009; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/eej.20707
Surge characteristics of a twisted pair
Authors: Kato Shohei , Solaiman Md.
Published: February 2009

We used the method of moments (MoM), which is a numerical electromagnetic field computation method, to study the surge characteristics of twisted pair single‐phase electric power lines. The results show that wires stranded with less than several turns per meter have almost the same surge characteristics as parallel lines, but the surge impedance decreases in tens of % when the number of strands increases. To verify the simulation results, we measured the surge characteristics of a model line of twisted pair experimentally, and there is good accordance between them. It is possible to simulate the surge in twisted pair covered with polymer dielectric insulators by MoM.

Moreover, we studied the surge characteristics of twisted pair which is inserted into a metal tube. According to the results, the effect of the strand is smaller than that in free space without the metal pipe. There are two propagation modes in common mode: fast surge and slow surge. Few influences of the number of strands on the surge velocity occur in the fast propagation surge, but the increase of the surge impedance and the slowdown of the propagation speed are caused by twining in the slow propagation mode. © 2009 Wiley Periodicals, Inc. Electr Eng Jpn, 167(3): 1–9, 2009; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/eej.20737
Increase of static electrification in an aged oil‐immersed transformer
Authors: Kobayashi Takayuki , Yajima Kouji , Yamada Shin , Amimoto Tsuyoshi , Hosokawa Noboru
Published: February 2009

Increase of static electrification activity and discharge generation was experienced during the service operation of an aged power transformer. The transformer oil had high sulfide and sulfoxide contents and was liable to show high ECT value after aging. However, there was no apparent increase in standard ECT (electrostatic charging tendency) measurement of the insulating oil and, therefore, deterioration of pressboard was suspected as the cause of the increase. The ECT tests with aged oil and pressboard sampled from the aged transformer were insufficient to demonstrate the increase in static electrification for the aged transformer. On the other hand, the results suggested a possibility that increase in static electrification can be caused by adsorption of some deterioration compound in the aged oil to the pressboard. In order to make more effective evaluation to the transformer insulation, potential measurement on the pressboard in the oil duct was carried out. The experimental results demonstrated strong increase of the accumulated charge by the aged pressboard, which suggested effectiveness of potential measurement for the assessment of static electrification in transformers. The device of potential measurement for practical use was designed by reducing the necessary amount of oil sampling. © 2009 Wiley Periodicals, Inc. Electr Eng Jpn, 167(3): 10–19, 2009; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/eej.20789
Novel Gallium Complexes with Malonic Diester Anions as Molecular Precursors for the MOCVD of Ga2O3 Thin Films
Authors: Hellwig Malte , Xu Ke , Barreca Davide , Gasparotto Alberto , Winter Manuela , Tondello Eugenio , Fischer Roland A. , Devi Anjana
Published: February 2009

Five different homoleptic gallium complexes with malonic diester anions [Ga(ROCOCHOCOR)3] [R = Me (1), Et (2), iPr (3), tBu (4) and SiMe3 (5)] have been synthesised and characterised by 1H and 13C NMR, IR spectroscopy, electron ionisation mass spectrometry (EI‐MS), and single‐crystal X‐ray diffraction. The thermal properties of the obtained compounds were evaluated by thermogravimetric studies to assess their suitability as precursors for the metal‐organic chemical vapour deposition (MOCVD) of Ga2O3 thin films. MOCVD of Ga2O3 thin films was carried out starting from compound 2 in light of the promising features of this precursor. The as‐deposited layers are amorphous and can be transformed into the monoclinic β‐Ga2O3 phase upon annealing at 1000 °C ex situ. The film morphology was studied by scanning electron microscopy (SEM), and its composition was investigated by energy‐dispersive X‐ray spectroscopy (EDXS) and X‐ray photoelectron spectroscopy (XPS). Almost stoichiometric Ga2O3 thin films with low levels of carbon incorporation were obtained.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)
Pseudoanguillosporin A and B: Two New Isochromans Isolated from the Endophytic Fungus Pseudoanguillospora sp.
Authors: Kock Ines , Draeger Siegfried , Schulz Barbara , Elsässer Brigitta , Kurtán Tibor , Kenéz Ágnes , Antus Sándor , Pescitelli Gennaro , Salvadori Piero , Speakman John‐Bryan , Rheinheimer Joachim , Krohn Karsten
Published: February 2009

Two new isochromans named pseudoanguillosporin A (2a) and B (3), together with the known cephalochromin (1), were isolated from Pseudoanguillospora sp. The C‐2 absolute configuration of 2a and 3 was deduced from its CD spectrum by the isochroman helicity rule, supported by TDDFT CD calculations. The absolute configuration of the sec‐hydroxyl group of 3 was determined by the Mosher NMR method from the MPA esters of its methylated derivative. The axial chirality of 1 was assigned through exciton analysis of its CD spectrum and confirmed by ZINDO CD calculations. The metabolites showed broad antimicrobial activities.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)
Benchmark and Solvent‐Free Preparation of Sulfonium Salt Based Electrophilic Trifluoromethylating Reagents
Authors: Macé Yohan , Raymondeau Benoit , Pradet Charlotte , Blazejewski Jean‐Claude , Magnier Emmanuel
Published: February 2009

Here we describe work devoted to the one‐pot preparation of electrophilic trifluoromethylating reagents. The first part describes a reappraisal of our earlier experimental conditions and leads to an improved protocol that avoids the use of solvent and allows better yields. The second part carefully studies the behavior of biaryl substrates, whose structures can drive the reaction through the formation of original noncyclic or tricyclic dibenzothiophenium salts. New compounds were tested, in a standard reaction with aniline, for their trifluoromethylating power and revealed equivalent or improved reactivity relative to that of existing reagents. Furthermore, contrary to common knowledge, the presence of electron‐donating methyl groups gave reagents with very high activity.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)
Dynamic Diels–Alder Reactions of 9,10‐Dimethylanthracene: Reversible Adduct Formation, Dynamic Exchange Processes and Thermal Fluorescence Modulation
Authors: Reutenauer Philippe , Boul Peter J. , Lehn Jean‐Marie
Published: February 2009

Studies of the Diels–Alder reactions between 9,10‐dimethylanthracene and cyano‐functionalized dienophiles led to the identification and characterization of new dynamic systems under ambient conditions. Among these dienophiles were tricyanoethynylethylene derivatives, which gave access to reversible thermal switching of fluorescent properties through binding to and release of the dimethylanthracene partner. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)
Numerical collapse simulation of large‐scale structural systems using an optimization‐based algorithm
Authors: Sivaselvan Mettupalayam V. , Lavan Oren , Dargush Gary F. , Kurino Haruhiko , Hyodo Yo , Fukuda Ryusuke , Sato Kiochi , Apostolakis Georgios , Reinhorn Andrei M.
Published: February 2009

A new algorithm for nonlinear dynamic simulation of structures is presented. The algorithm is based on a mixed Lagrangian approach described by Sivaselvan and Reinhorn (J. Eng. Mech. (ASCE) 2006; 132(8):795–805). The algorithm developed in this paper is for the simulation of large‐scale structural systems. The algorithm is applicable to a wide class of structural systems whose constituent material or component behavior can be derived from a stored energy function and a dissipation potential. The algorithm is based on the fact that for such systems, when using a certain class of time‐discretization schemes to numerically compute the system response, the incremental problem of computing the system state at the next sample time knowing the current state and the input is one of convex minimization. As a result, the algorithm possesses excellent convergence characteristics. It is also applicable to geometric nonlinear problems. The implementation of the algorithm is described, and its applicability to the collapse analysis of large‐scale structures is demonstrated through numerical examples. Copyright © 2009 John Wiley & Sons, Ltd.
Waiting times and socioeconomic status among elderly Europeans: evidence from SHARE
Authors: Siciliani Luigi , Verzulli Rossella
Published: February 2009

Waiting times for specialist consultation and non‐emergency surgery are often considered an equitable rationing mechanism in the public healthcare sector, because access to care is not based on socioeconomic status. This study tests empirically this claim using data from the Survey of Health, Ageing and Retirement in Europe (SHARE). The sample includes nine European countries: Austria, Denmark, France, Germany, Greece, Italy, the Netherlands, Spain and Sweden. For specialist consultation, we find that individuals with high education experience a reduction in waiting times of 68% in Spain, 67% in Italy and 34% in France (compared with individuals with low education). Individuals with intermediate education report a waiting‐time reduction of 74% in Greece (compared with individuals with low education). There is also evidence of a negative and significant association between education and waiting times for non‐emergency surgery in Denmark, the Netherlands and Sweden. High education reduces waits by 66, 32 and 48%, respectively. We also find income effects, although generally modest. An increase in income of 10 000 Euro reduces waiting times for specialist consultation by 8% in Germany and waiting times for non‐emergency surgery by 26% in Greece. Surprisingly, an increase in income of 10 000 Euro increases waits by 11% in Sweden. Copyright © 2009 John Wiley & Sons, Ltd.
Pathways of runoff and sediment transfer in small agricultural catchments
Authors: Deasy C. , Brazier R. E. , Heathwaite A. L. , Hodgkinson R.
Published: February 2009

Simultaneous field monitoring of runoff and suspended sediment loads from a 30 ha, artificially‐drained, mixed‐agricultural catchment in Herefordshire, UK indicates field drains are the dominant pathway for the transfer of runoff and sediment to the stream. Surface runoff pathways draining 6·2% of the catchment area transported around 1% of the catchment sediment load, while subsurface runoff in field drains draining 26·5% of the catchment transported around 24% of the sediment load. The explanations offered here for the dominance of drainflow—the spatial limitation of surface runoff generation and low hillslope‐stream connectivity of surface runoff compared with subsurface runoff—are also likely to apply to other artificially‐drained lowland agricultural catchments in the UK. These catchments are usually on poorly‐drained soils, and land management can have a considerable effect on the operation of runoff pathways and the transfer of sediment from hillslope to stream. As a result, subsurface inputs may also dominate sediment transfers in other underdrained catchments. The focus on sediment and pollutant losses via surface runoff pathways means that pollution inputs from subsurface, preferential pathways have been unfairly neglected, and it may be more important to focus on subsurface sediment and sediment‐associated pollution inputs for mitigation rather than inputs from surface pathways. Copyright © 2009 John Wiley & Sons, Ltd.
FGFR4 Gly388Arg polymorphism may affect the clinical stage of patients with lung cancer by modulating the transcriptional profile of normal lung
Authors: Falvella Felicia S. , Frullanti Elisa , Galvan Antonella , Spinola Monica , Noci Sara , De Cecco Loris , Nosotti Mario , Santambrogio Luigi , Incarbone Matteo , Alloisio Marco , Calabrò Elisa , Pastorino Ugo , Skaug Vidar , Haugen Aage , Taioli Emanuela , Dragani Tommaso A.
Published: February 2009

The association of the fibroblast growth factor receptor 4 (FGFR4) Gly388Arg polymorphism with clinical stage and overall survival in a series of 541 Italian lung adenocarcinoma (ADCA) patients indicated a significantly decreased survival in patients carrying the rare Arg388 allele as compared to that in Gly/Gly homozygous patients [hazard ratio (HR) = 1.5; 95% confidence interval (CI) 1.1–1.9], with the decrease related to the association of the same polymorphism with clinical stage (HR = 1.8, 95% CI 1.3–2.6). By contrast, no significant association was detected in small series of either Norwegian lung ADCA patients or Italian lung squamous cell carcinoma (SQCC) patients. Single nucleotide polymorphisms of known FGFR4 ligands expressed in lung (FGF9, FGF18 and FGF19) were not associated with clinical stage or survival and showed no interaction with FGFR4. Analysis of gene expression profile in normal lungs according to FGFR4 genotype indicated a specific transcript pattern associated with the allele carrier status, suggesting a functional role for the FGFR4 polymorphism already detectable in normal lung. These findings confirm the significant association of the FGFR4 Gly388Arg polymorphism with clinical stage and overall survival in an Italian lung ADCA population and demonstrate a FGFR4 genotype‐dependent transcriptional profile present in normal lung tissue. © 2009 UICC
Correlation among pathology, genetic and epigenetic profiles, and clinical outcome in oligodendroglial tumors
Authors: Kuo Lu‐Ting , Kuo Kuang‐Ting , Lee Ming‐Jang , Wei Chih‐Chun , Scaravilli Francesco , Tsai Jui‐Chang , Tseng Ham‐Min , Kuo Meng‐Fai , Tu Yong‐Kwang
Published: February 2009

Recent studies have revealed a correlation between specific genetic changes, such as loss of chromosome 1p and 19q, and sensitivity of oligodendroglial neoplasm to radiotherapy and chemotherapy; epigenetic changes also play an important role in some tumors. In this retrospective study, we analyzed chromosomal alterations in 17 loci and promoter methylation status of 8 tumor‐related genes in 49 oligodendroglial tumors (29 WHO grade II and 11 WHO grade III oligodendrogliomas; 7 WHO grade II and 2 WHO grade III oligoastrocytomas) using quantitative microsatellite analysis and methylation‐specific polymerase chain reaction and correlated this information with clinical data. We also performed immunohistochemical stains for Ki‐67 and O (6)‐methyl guanine‐DNA methyl transferase. Our results showed that the frequency of deletions in regions on 1p, 9p, 10q, 17p and 19q were 71.4%, 26.5%, 6.1%, 69.4% and 89.8%, respectively. Promoter methylation was detected in p14, p15, p16, p53, p73, PTEN, MGMT and RASSF1A genes in 24.5%, 6.1%, 46.9%, 0%, 6.1%, 42.9%, 53.1% and 77.6% of tumors, respectively. Statistical analysis identified that 9p22 loss, p73 methylation and p15 methylation were independently associated with reduced overall survival, and Ki‐67 labeling index (LI) ≥ 5%, 9p22 loss, no loss of 19q, p73 methylation, p14 methylation and unmethylated MGMT predicted shorter progression‐free survival. Our findings suggest that the frequent deletion and hypermethylation of tumor‐related genes may represent a mechanism of tumor development and progression and emphasize the importance of defining new molecular markers for predicting prognosis, tumor recurrence and therapeutic response in cancer management. © 2009 UICC
Reduction of Akt2 inhibits migration and invasion of glioma cells
Authors: Zhang Baogang , Gu Feng , She Chunhua , Guo Hua , Li Wenliang , Niu Ruifang , Fu Li , Zhang Ning , Ma Yongjie
Published: February 2009

Malignant gliomas have a tendency to invade diffusely into surrounding healthy brain tissues, thereby precluding their successful surgical removal. The serine/threonine kinase Akt2 is well known as an important regulator of cell survival and growth. In this study, we show that siRNA‐mediated depletion of Akt2 inhibited migration and invasion of glioma cells. In addition, we demonstrate the mechanisms by which Akt2 functions to promote cell migration and invasion. Phosphorylation of cofilin, a critical step of actin polymerization, and phosphorylation of Girdin, essential for the integrity of the actin cytoskeleton and cell migration, were impaired. Furthermore, epidermal growth factor‐induced ACAP1 phosphorylation and integrin β1 phosphorylation were also blocked, consistent with defects in adhesion. Thus, Akt2 regulates both cell adhesion and cytoskeleton rearrangement during migration. Decreased MMP‐9 expression in Akt2 knocked‐down glioma cells was subsequently confirmed by Western blotting, consistent with the decreased invasion in vitro and in vivo. These results suggest that Akt2 contributes to glioma cells migration and invasion by regulating the formation of cytoskeleton, influencing adhesion and increasing expression of MMP‐9. Our immunohistochemistry results by using human gliomas tissue sections also indicated that Akt2 expression was closely related with the malignancy of gliomas. This is coincident with our in vivo and in vitro results from cell lines. All of these results indicate that Akt2 is a critical factor in gliomas invasion. This study identifies that Akt2 is a potentially antiinvasion target for therapeutic intervention in gliomas. © 2009 UICC
p16INK4a expression in cytology of ascites and response to chemotherapy in advanced ovarian cancer
Authors: Goto Tomoko , Takano Masashi , Hirata Junko , Kohno Toshiyuki , Ohtsuka Shigenori , Fujiwara Keiichi , Tsuda Hitoshi
Published: February 2009

The aim of this study is to investigate p16INK4a expression by immunocytochemistry for ascites in advanced ovarian cancer and explore the possibility to predict chemotherapeutic response and prognosis. The immunocytochemical study was performed on cytology of ascites obtained from 37 Stage III or Stage IV ovarian cancer patients with measurable disease before platinum/taxane‐based first‐line chemotherapy following primary cytoreductive surgery or as neoadjuvant chemotherapy. Twenty‐one of 21 (100%) responders and 6 of 16 (44%) nonresponders showed p16INK4a immunopositivity (p < 0.001). Immunopositivity was frequently observed in serous adenocarciomas (17 of 18, 94%). Overall survival was significantly better in immunopositive cases compared with immunonegative cases (p = 0.0006). For subcellular localization, cytoplasm was diffusely positive in immunopositive cases (n = 27), 12 of which showed stronger nuclear immunostaining and demonstrated superior overall survival. In vitro expression of p16INK4a protein was also examined for both parent chemosensitive and acquired chemoresistant ovarian cancer cell lines. Chemosensitive KF28 parent cells showed stronger nuclear staining compared with chemoresistant KFr13Tx cells showing stronger cytoplasmic staining by immunocytochemistry, which were also confirmed by western blotting. Our data suggest that p16INK4a expression in cytology of ascites is a candidate marker in prediction of the primary response to chemotherapy and prognosis. © 2009 UICC
Pml and TAp73 interacting at nuclear body mediate imatinib‐induced p53‐independent apoptosis of chronic myeloid leukemia cells
Authors: Liu Jin‐Hwang , Liu Chin‐Cheng , Yen Chueh‐Chuan , Gau Jyh‐Pyng , Wang Wei‐Shu , Tzeng Cheng‐Hwai
Published: February 2009

Bcr‐abl signals for leukemogenesis of chronic myeloid leukemia (CML) and activates ras. Since the function of promyelocytic leukemia protein (pml) is provoked by ras to promote apoptosis and senescence in untransformed cells, the function is probably masked in CML. Imatinib specifically inhibits bcr‐abl and induces apoptosis of CML cells. As reported previously, p53wild CML was more resistant to imatinib than that lacking p53. Here, we searched for an imatinib‐induced p53 independent proapoptotic mechanism. We found imatinib up‐regulated phosphorylation of p38 mitogen‐activated protein kinase (MAPK), checkpoint kinase 2 (chk2) and transactivation‐competent (TA) p73; expression of pml and bax; formation of PML‐nuclear body (NB); and co‐localization of TAp73/PML‐NB in p53‐nonfunctioning K562 and p53mutant Meg‐01 CML cells, but not in BCR‐ABL‐ HL60 cells. In K562 cells, with short interfering RNAs (siRNAs), knockdown of pml led to dephosphorylation of TAp73. Knockdown of either pml or TAp73 abolished the imatinib‐induced apoptosis. Inhibition of p38 MAPK with SB203580 led to dephosphorylation of TAp73, abolishment of TAp73/PML‐NB co‐localization, and the subsequent apoptosis. Conversely, interferon α‐2a (IFNα), which increased phosphrylated TAp73 and TAp73/PML‐NB co‐localization, increased additively apoptosis with imatinib. The imatinib‐induced TAp73/PML‐NB co‐localization was accompanied by co‐immpunoprecipitation of TAp73 with pml. The imatinib‐induced co‐localization was also found in primary CML cells from 3 of 6 patients, including 2 with p53mutant and one with p53wild. A novel p53‐independent proapoptotic mechanism using p38 MAPK /pml/TAp73 axis with a step processing at PML‐NB and probably with chk2 and bax being involved is hereby evident in some imatinib‐treated CML cells. © 2009 UICC
Enhancement of immunogenicity of a therapeutic cervical cancer DNA‐based vaccine by co‐application of sequence‐optimized genetic adjuvants
Authors: Öhlschläger Peter , Quetting Michael , Alvarez Gerardo , Dürst Matthias , Gissmann Lutz , Kaufmann Andreas M.
Published: February 2009

Treatment of patients with cervical cancer by conventional methods (mainly surgery, but also radiotherapy and chemotherapy) results in a significant loss in quality of life. A therapeutic DNA vaccine directed to tumor‐specific antigens of the human papilloma virus (HPV) could be an attractive treatment option. We have developed a nontransforming HPV‐16 E7‐based DNA vaccine containing all putative T cell epitopes (HPV‐16 E7SH). DNA vaccines, however, are less immunogenic than protein‐ or peptide‐based vaccines in larger animals and humans. In this study, we have investigated an adjuvant gene support of the HPV‐16 E7SH therapeutic cervical cancer vaccine. DNA encoded cytokines (IL‐2, IL‐12, GM‐CSF, IFN‐γ) and the chemokine MIP1‐α were co‐applied either simultaneously or at different time points pre‐ or post‐E7SH vaccination. In addition, sequence‐optimized adjuvant genes were compared to wild type genes. Three combinations investigated lead to an enhanced IFN‐γ response of the induced T cells in mice. Interestingly, IFN‐γ secretion of splenocytes did not strictly correlate with tumor response in tumor regression experiments. Gene‐encoded MIP‐1α applied 5 days prior to E7SH‐immunization combined with IFN‐γ or IL‐12 (3 days) or IL‐2 (5 days) postimmunization lead to a significantly enhanced tumor response that was clearly associated with granzyme B secretion and target cells lysis. Our results suggest that a conditioning application and combination with adjuvant genes may be a promising strategy to enhance synergistically immune responses by DNA immunization for the treatment of cervical cancer. © 2009 UICC
Accelerating molecular dynamic simulation on graphics processing units
Authors: Friedrichs Mark S. , Eastman Peter , Vaidyanathan Vishal , Houston Mike , Legrand Scott , Beberg Adam L. , Ensign Daniel L. , Bruns Christopher M. , Pande Vijay S.
Published: February 2009

We describe a complete implementation of all‐atom protein molecular dynamics running entirely on a graphics processing unit (GPU), including all standard force field terms, integration, constraints, and implicit solvent. We discuss the design of our algorithms and important optimizations needed to fully take advantage of a GPU. We evaluate its performance, and show that it can be more than 700 times faster than a conventional implementation running on a single CPU core. © 2009 Wiley Periodicals, Inc. J Comput Chem, 2009
Baculovirus transduction of chondrocytes elicits interferon‐α/β and suppresses transgene expression
Authors: Lee Hsiao‐Ping , Matsuura Yoshiharu , Chen Huang‐Chi , Chen Yen‐Lin , Chuang Ching‐Kuang , Abe Takayuki , Hwang Shiaw‐Min , Shiah Hsiao‐Chiao , Hu Yu‐Chen
Published: February 2009

Background

Baculovirus is an effective vector for gene delivery into primary chondrocytes and repeated baculovirus transduction (i.e. supertransduction) appears to be promising for prolonging transgene expression, but how supertransduction may influence baculovirus‐mediated gene delivery is unknown.

Methods

We first investigated whether prior baculovirus transduction suppressed the ensuing transgene expression mediated by the supertransduced baculovirus, and then examined whether baculovirus triggered the expression of various cytokines. Whether interferon‐α and ‐β (IFN‐α/β) suppressed the transgene expression as well as the pivotal step responsible for the attenuated transgene expression were examined.

Results

Baculovirus transduction of chondrocytes elicited an immediate yet transient expression of IFN‐α/β, which repressed the transgene expression in a dose‐dependent manner. The attenuation was observed for transgene expression driven by different promoters and resulted neither from internalization or nuclear import of baculovirus. Moreover, the attenuation was alleviated if supertransduction was performed when IFN‐α/β responses diminished. Baculovirus transduction also triggered the expression of tumor necrosis factor‐α and interleukin (IL)‐6, but not IL‐1β. Despite the induction of these responses, supertransduction of chondrocytes with a baculovirus expressing bone morphogenetic protein‐2 successfully enhanced the chondrogenic differentiation and matrix synthesis.

Conclusions

Baculovirus transduction of primary chondrocytes elicits antiviral effects that suppress transgene expression. Nonetheless, baculovirus supertransduction comprises a feasible approach to extend transgene expression for cartilage engineering. Copyright © 2009 John Wiley & Sons, Ltd.
Simple setup for hybrid coherent Raman microspectroscopy
Authors: Peng Jiahui , Pestov Dmitry , Scully Marlan O. , Sokolov Alexei V.
Published: February 2009

We demonstrate a femtosecond‐oscillator‐based system for coherent anti‐Stokes/Stokes Raman scattering microscopy, wherein impulsive Raman excitation is combined with narrowband, time‐delayed, and therefore, background‐free probing. We show that this simple technique can be used for microscopic imaging with chemical contrast. Copyright © 2009 John Wiley & Sons, Ltd.
Four‐wave mixing spectroscopy of hydration layers in biopolymers and carbon nanotubes aqueous solutions
Authors: Bunkin A.F. , Pershin S.M.
Published: February 2009

We have studied the water spectrum modification in the presence of biomolecules (protein, DNA) and single wall carbon nanotube (SWNT) at low concentration, ∼10 mg/ml and ∼0.1 µg/ml respectively, by four‐wave mixing (FWM) spectroscopy in the ranges 0.1–10 cm−1 and 75–95 cm−1. A comparison of distilled water and aqueous solutions' FWM spectra shows a considerable growth in the intensity of low wavenumber Raman modes in solution. These modes are attributed to rotational transitions of H2O and H2O2 molecules. It was established that in the biopolymer's aqueous solutions the ortho‐isomer rotational lines' intensity increases by a factor of ∼6. In contrast, the para‐isomer's lines are considerably suppressed. In the SWNT suspension the spin‐selective interaction was not observed. The shifting of Brillouin resonances in the opposite direction in biomolecules and SWNT suspension in comparison with water was observed and discussed. Copyright © 2009 John Wiley & Sons, Ltd.
Vibrational study of A3In2B″O9 (A = Ba, Sr; B″ = U, W) double perovskites
Authors: Silva E. N. , Ayala A. P. , Guedes I. , Larregola S. A. , Pinacca R. M. , Viola M. del C. , Pedregosa J. C.
Published: February 2009

Raman scattering and infrared transmittance techniques were used to investigate the room‐temperature phonon spectra of the polycrystalline Ba3In2UO9, Sr3In2UO9, Ba3In2WO9 and Sr3In2WO9 double perovskites. Although X‐ray diffraction has shown that both Ba3In2UO9 and Ba3In2WO9 crystallize in a disordered cubic (Pm3m − Oh1) structure with one formula unit per unit cell (Z = 1), Raman measurements revealed that both Ba3In2UO9 and Ba3In2WO9 compounds should exhibit a 1:1 ordered domains with Fm3m symmetry, embedded in the Pm3m matrix. Observation of a ν1‐like vibration of the InO6 octahedron reflects the occurrence of a two‐phonon‐like behavior due to the intrinsic occupational disorder at octahedral symmetry sites. Assignment of most of the Raman and infrared phonons is also given. Copyright © 2009 John Wiley & Sons, Ltd.
Use of polymer fiber stationary phases for liquid chromatography separations: Part II – applications
Authors: Marcus R. Kenneth
Published: February 2009

The idea of using polymer fibers as stationary phases for LC is not a new one. There are in fact a number of good reasons for which they should be considered. Presented here are a number of applications of polymer fiber stationary phases for chemical separations. Fibers placed in columns are employed in three basic formats: staple, whole fabrics, and aligned fibers. Natural and synthetic fibers have found use in a variety of chromatographic modes including RP, size exclusion chromatography (SEC), and IEC. Consistent among these examples are the ability to employ high mobile phase flow rates with minimal back pressures. The most promising applications are in the separation of macromolecules, where the mass transfer characteristics of the phases result in the ability to run at high linear velocities without penalty. This bodes well in particular for process applications.
Oxidative stress due to anesthesia and surgical trauma: Importance of early enteral nutrition
Authors: Kotzampassi Katerina , Kolios George , Manousou Pinelopi , Kazamias Pantelis , Paramythiotis Daniil , Papavramidis Theodosis S. , Heliadis Stavros , Kouroumalis Elias , Eleftheriadis Efthimios
Published: February 2009

Anesthesia and surgical trauma are considered major oxidative and nitrosative stress effectors resulting in the development of SIRS. In this study we evaluated the usefulness of early enteral nutrition after surgical trauma. Sixty male Wistar rats were subjected to midline laparotomy and feeding‐gastrostomy. Twenty of these rats served as controls after recovering from the operation stress. The remaining rats received, through gastrostomy, enteral nutrition or placebo‐feeding for 24 h. Oxidative stress markers and CC chemokine production were evaluated in rat serum and liver tissue. The operation itself was found to increase nitric oxide (NO) and malondialdehyde (MDA) and to decrease superoxide dismutase (SOD) and glutathione peroxidase (GSH‐Px), as well as liver tissue energy charge (EC) in relation to controls. The rats receiving enteral feeding exhibited statistically significantly lower levels of NO and MDA, and higher levels of SOD, GSH‐Px, and liver EC, in relation to placebo feeding rats. The operation significantly increased the chemokines monocyte chemoattractant protein (MCP)‐1 and regulated upon activation, normal T‐cell expressed, and secreted (RANTES) in rat serum, while enteral nutrition caused a further significant increase in chemokine levels in serum. mRNA chemokine expression in liver was increased in a similar pattern. These findings indicate that early enteral feeding might play an important role after surgery ameliorating oxidative stress, affecting positively the hepatic EC and regulating, via chemokine production, cell trafficking, and healing process.