bluuebunny/crossref_metadata_2025 huggingface dataset:
Synthesis of Unusually Substituted Ureas Starting from Bis(1,3,4‐thiadiazolo)‐1,3,5‐triazinium Halides via Oxo‐imidothioate Zwitterions
Authors: Schulz Martin , Michnacs Marion , Görls Helmar , Anders Ernst
Published: July 2009

Bis(1,3,4‐thiadiazolo)‐1,3,5‐triazinium halides 1 can be converted into various products such as guanidines or bis(azolyl)alkanes. However, they also react with hydroxide ions in aqueous solution to form novel heterocyclic‐substituted ureas 2a–i. The yields were increased from moderate to good or excellent in the presence of excess guanidine 3. The assumption that hydrogen‐bonded intermediate encounter complexes EC are formed gives a reasonable explanation for the observed reaction path. The molecular structures of some of the crystalline products 2 were determined by X‐ray analysis. Furthermore, with copper(II) a dinuclear complex 8 is formed with the two metal ions in a distorted octahedral environment; a water molecule acts as a bridging ligand between the CuII ions. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)
Efficient Regiospecific Conjugated Ring Fusion in N‐Confused Porphyrin
Authors: Chmielewski Piotr J. , Maciołek Justyna , Szterenberg Ludmiła
Published: July 2009

Acid‐catalyzed exocyclic ring formation in meso‐tetrakis(3′,5′‐dimethoxyphenyl)‐2‐aza‐21‐carbaporphyrin takes place regioselectively between the external carbon atom of the confused pyrrole and the ortho‐carbon atom of the adjacent meso‐aryl group. The ring fusion strongly alters the spectroscopic properties of the macrocycle, but its aromaticity is preserved, as shown by NMR spectroscopy as well as DFT calculations. A tendency to self‐associate is observed for partially protonated and nickel(II)‐metalated systems. A novel silver(I)‐bridged dimer is formed in the reaction of the fused carbaporphyrin with AgBF4. Cyclic voltammetry studies of this system indicate an interaction between the subunits. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)
Syntheses and15N NMR Spectra of Iminodiaziridines – Ring‐Expansions of 1‐Aryl‐3‐iminodiaziridines to 1H‐ and 3aH‐Benzimidazoles, 2H‐Indazoles, and 5H‐Dibenzo[d,f][1,3]diazepines
Authors: Quast Helmut , Ross Karl‐Heinz , Philipp Gottfried , Hagedorn Manfred , Hahn Harald , Banert Klaus
Published: July 2009

Iminodiaziridines are synthesized by (i) 1,3‐dehydrochlorination with potassiumtert‐butoxide ofN‐chloroguanidines, generated in situ fromN,N′,N″‐substituted guanidines withtert‐butyl hypochlorite, and (ii) base‐mediated 1,3‐elimination of sulfuric acid fromN,N′,N″‐substituted hydroxyguanidineO‐sulfonic acids. At elevated temperatures, (alkylimino)diaziridines undergo valence isomerization by 1,3‐shift, [2+1] cycloelimination to afford isocyanides and diazenes, and ring‐opening elimination to yield alkylideneguanidines.N′‐Aryl‐N‐hydroxyguanidineO‐sulfonic acids furnish (N‐arylimino)diaziridines, but no 1‐aryl‐3‐iminodiaziridines, instead giving rearranged isomers. Precursors containing perdeuteratedtert‐butyl groups give rearranged products that show complete scrambling. This indicates that 1‐aryl‐3‐iminodiaziridines are intermediates that undergo very rapid degenerate valence isomerization. Provided that theortho‐aryl positions are substituted, high yields of (arylimino)diaziridines are obtained, along with 2‐imino‐2,3‐dihydro‐3aH‐benzimidazoles. Otherwise, 2‐amino‐1H‐benzimidazoles and strongly fluorescent 3‐amino‐2H‐indazoles, originating from rearrangements of the elusive 1‐aryl‐3‐iminodiaziridines, predominate.N′,N″‐Diaryl‐N‐hydroxyguanidineO‐sulfonic acids give only rearranged products: a 2‐amino‐1H‐benzimidazole and a 6‐amino‐5H‐dibenzo[d,f][1.3]diazepine if aryl = phenyl, or a 2‐imino‐2,3‐dihydro‐3aH‐benzimidazole if aryl = mesityl. 3aH‐Benzimidazoles slowly dimerize through Diels–Alder reactions.15N NMR signals were assigned to thesynandantiring nitrogen atoms of iminodiaziridines with the help of a combination of homonuclear NOE and HN‐HMBC or HN‐gHMBC experiments. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)
Towards Long‐Living Metathesis Catalysts by Tuning the N‐Heterocyclic Carbene (NHC) Ligand on Trifluoroacetamide‐Activated Boomerang Ru Complexes
Authors: Clavier Hervé , Caijo Fréderic , Borré Etienne , Rix Diane , Boeda Fabien , Nolan Steven P. , Mauduit Marc
Published: July 2009

The synthesis and characterization of three novel trifluoromethylamido‐containing “boomerang” precatalysts bearing various N‐heterocyclic carbene (NHC) ligands are reported. Comparative kinetic and stability studies show the significant effect of the NHC on the catalyst reaction profile. An investigation of the reaction scope for diverse metathesis transformations has allowed us to establish the influence of the NHC on catalyst activity, especially as a function of substrate steric bulk. The excellent stability of one of the novel precatalysts is disclosed, and allowed for its recovery at the end of catalytic reactions. Large‐scale ring‐closing metathesis, enyne‐metathesis and cross‐metathesis experiments have revealed the recoverability of the catalyst. ICP‐MS analyses of the synthesized products reveal Ru contamination levels of less than 2.5 ppm.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)
Facile Access to Fluorinated Aryl and Vinyl Ethers through Copper‐Catalysed Reaction of Fluoro Alcohols (Eur. J. Org. Chem. 21/2009)
Authors: Vuluga Daniela , Legros Julien , Crousse Benoit , Bonnet‐Delpon Danièle
Published: July 2009

The cover picture shows the reaction between fluoro alcohols and aryl halides in the presence of copper iodide to afford fluoro ethers. The incorporation of the trifluoroethoxy moiety generally brings lipophilicity and metabolic stability to the substrate, and this group is found in numerous pharmaceuticals such as Flecainide. Details are discussed in the article by J. Legros, B. Crousse et al. on p. 3513 ff. The Région Ile‐de‐France is kindly acknowledged for support.
Women's reactions to ingroup members who protest discriminatory treatment: The importance of beliefs about inequality and response appropriateness
Authors: Garcia Donna M. , Schmitt Michael T. , Branscombe Nyla R. , Ellemers Naomi
Published: July 2009

Our goal was to identify factors that shape women's responses to ingroup members who protest gender discrimination. We predicted and found that women who perceived gender discrimination as pervasive regarded a protest response as being more appropriate than a no protest response and expressed greater liking and less anger towards a female lawyer who protested rather than did not protest an unfair promotion decision. Further, beliefs about the appropriateness of the response to discrimination contributed to evaluations of the protesting lawyer. Perceptions that the complaint was an appropriate response to the promotion decision led to more positive evaluations of an ingroup discrimination protester. Copyright © 2009 John Wiley & Sons, Ltd.
Reopening the study of extreme social behaviors: Obedience to authority within an immersive video environment
Authors: Dambrun Michaël , Vatiné Elise
Published: July 2009

In this study, we used a paradigm similar to the one used by Milgram in his classic obedience study, using an immersive video environment. We manipulated the victim's degree of visibility and his ethnicity. When the victim was hidden, the level of obedience we obtained was similar to Milgram's. Replicating previous findings observed in real environments, participants were more obedient when the victim was hidden than when he was visible, and the more obedient participants negated their own responsibility by projecting responsibility on both the victim and the experimenter. State‐anger and right‐wing authoritarianism (RWA) emerged as two significant predictors of the level of obedience. Illustrating an underlying process of racial‐dehumanization, participants reported less anxiety and distress when the victim was a North African than when the victim was of the same racial origin as the participant. These results underscore the usefulness of using immersive environments when studying extreme social behaviors. Copyright © 2009 John Wiley & Sons, Ltd.
A group just like me: The moderating role of conservation values on social projection
Authors: Amit Adi , Roccas Sonia , Meidan Michal
Published: July 2009

We examined the moderating role of personal values on social projection. Study 1 was conducted prior to the 1999 Israeli elections among activists of the Center party, a newly established centrist party. The more importance activists attributed to conservation values (values that emphasize stability and certainty) the more they projected their political views to their party. Study 2 was conducted prior to the 2003 Israeli elections among students with varied attitudes toward the Kadima party, another newly established centrist party. Conservation values interacted with support for the Kadima party in their effect on social projection: The more importance participants attributed to conservation values, the more positive was the relationship between support for the party and social projection. In Study 3, we examined the role of conservation values in an experimental study in which participants were members of a virtual team: Raising the accessibility of conservation values resulted in higher levels of social projection. Taken together, findings indicate that emphasizing conservation values leads to greater social projection. Copyright © 2009 John Wiley & Sons, Ltd.
The role of perpetrator similarity in reactions toward innocent victims
Authors: Bal Michèlle , van den Bos Kees
Published: July 2009

Building and extending on just world theory, this paper studies people's negative reactions to innocent victims of rape or sexual assault. Specifically, we focus on an as yet unexplored variable that may help to explain these reactions, namely whether the perpetrator of the crime was similar or dissimilar to people who observed what happened to the victim. Perpetrator similarity refers to whether the perpetrator belongs to the personal world of the observer or not, and in accordance with predictions derived from just world theory, findings of three studies reveal that especially men take more physical distance from an innocent victim (Study 1) and blame (Study 2) and derogate (Study 3) an innocent victim more when the perpetrator is similar to them as opposed to when the perpetrator is different from them. Implications are discussed. Copyright © 2009 John Wiley & Sons, Ltd.
Detection of autoantibodies against cyclophilin A and triosephosphate isomerase in sera from breast cancer patients by proteomic analysis
Authors: Tamesa Michiko Sato , Kuramitsu Yasuhiro , Fujimoto Masanori , Maeda Noriko , Nagashima Yukiko , Tanaka Toshiyuki , Yamamoto Shigeru , Oka Masaaki , Nakamura Kazuyuki
Published: July 2009

Much interest is presently being shown toward identifying markers for the detection of breast cancer. To detect autoantibodies that could represent diagnostic markers for breast cancer, we comprehensively analyzed serum autoantibodies showing immunoreactivity to proteins in tumor tissues of breast cancer. Tumor tissues were obtained from 40 patients with breast cancer, along with sera from 30 other patients with breast cancer and 22 healthy donors. Proteins from tumor tissues were separated by 2‐DE. After blotting onto PVDF membranes, tissue proteins were immunoblotted with sera from patients or healthy donors. By comparing each immunoblot pattern, three immunoreactive spots displayed stronger staining intensity with patient sera than with sera from healthy donors. The matched protein spots on 2‐DE gels were digested and used for LC‐MS/MS analysis, and identified as cyclophilin A (peptidyl‐prolylcis‐transisomerase A), triosephosphate isomerase and ubiquitin‐conjugating enzyme E2N. Immunoblot analysis was then performed using commercially available purified proteins, confirming the specificity of anti‐cyclophilin A and anti‐triosephosphate isomerase antibodies in sera from patients.
Rapid recovery of DNA from agarose gel slices by coupling electroelution with monolithic SPE
Authors: Yu Shengbing , Yang Shuixian , Zhou Ping , Zhou Ke , Wang Jing , Chen Xiangdong
Published: July 2009

An amino silica monolithic column prepared by in situ polymerization of tetraethoxysilane and N‐(β‐aminoethyl)‐γ‐aminopropyltriethoxysilane was firstly applied to recover DNA from agarose gel slices by coupling electroelution with monolithic SPE. DNA was electroeluted from the agarose gel slices onto the amino silica monolithic column. The DNA adsorbed on this monolithic column was then recovered using sodium phosphate solution at pH 10. The whole recovery procedure could be completed within 10 min because the use of amino silica monolithic column accelerated the DNA capture and facilitated the DNA release. Electroelution conditions, such as buffer pH, buffer concentration and applied voltage, were online optimized. The average yield for herring sperm DNA, pBR 322 DNA and λDNA recovered from 1.0% w/v agarose gel slices were 55±4, 50±6 and 42±7% (n=3), respectively. The polymerase chain reaction performance of pGM plasmid recovered from agarose gel slices demonstrated that the method could provide high‐quality DNA for downstream processes. The combination of electroelution with monolithic SPE allows a rapid, simple and efficient DNA recovery method. This technique is especially useful for applications that need to purify small starting amounts of DNA.
Separation of acidic and basic proteins by CE with CTAB additive and its applications in peptide and protein profiling
Authors: Liu Qian , Yang Yanmin , Huang Yan , Pan Chunfeng , Nie Zhou , Yao Shouzhuo
Published: July 2009

In this paper, we report a very simple but efficient cationic micellar CE method for protein analysis in complex samples without any modification for the capillary wall. It was found that increased concentration (≥2 mM) of CTAB additive in electrophoretic buffer can effectively suppress the wall adsorption of both acidic and basic proteins. The separation was improved with buffer pH decreasing from 6.0 to 3.0. By using a buffer containing 2 mM CTAB at pH 3.0, nine proteins with a wide range of pI values (4.7–11.0) were separated within 9 min with high efficiencies (>6×105 plates per meter) and good reproducibility (RSDs of migration time <0.8% for run‐to‐run assays) and recoveries (91.6–119.0%). This method was successfully applied to the analysis of complex biological samples, including plasma and red blood cells. Most importantly, we demonstrate the proteomic applications of the proposed method, including the analysis of tryptic digests of BSA and crude protein extracts from Escherichia coli cells. With simplicity, high efficiency, and good reproducibility, this method is promising for protein analysis in complex samples and may find its place in the future proteomic research.
Proteomic signature of reversine‐treated murine fibroblasts by 2‐D difference gel electrophoresis and MS: Possible associations with cell signalling networks
Authors: Fania Chiara , Anastasia Luigi , Vasso Michele , Papini Nadia , Capitanio Daniele , Venerando Bruno , Gelfi Cecilia
Published: July 2009

Recent advances in stem cell biology have demonstrated that terminally differentiated adult cells can be induced to de‐differentiate into progenitor cells (induced stem cells) upon proper stimuli. This has been achieved by the induced expression of key regulatory genes by retro‐ or lenti‐viral systems. On the other hand, synthetic “small molecules” can also induce de‐differentiation and may represent a potentially safer approach as compared with genetic manipulation. Along this line, a synthetic purine called “reversine” has been shown to induce the de‐differentiation of fibroblasts into mesenchymal stem‐cell‐like progenitors, which can be successively induced to differentiate into skeletal muscle, smooth muscle and bone cells. The mechanism whereby reversine is able to achieve de‐differentiation has yet to be clarified. In this context, we defined the protein changes induced by reversine treatment in murine fibroblasts by 2‐D difference gel electrophoresis, coupled with MS. Proteins involved in cytoskeletal and cell shape remodeling, RNA export, degradation, folding, stress control and ATP production were found to be remarkably changed after reversine treatment. Ingenuity pathway analysis (IPA) predicted that these protein pattern changes enabled to propose that about 40 proteins might be associated to several biological functional networks, including cellular assembly, cell signaling and cell death. Altogether our data confirm the intrinsic complexity of the de‐differentiation process induced by reversine and suggest more selected approaches to investigate the action mechanism of this small molecule.
Protein attachment onto silica surfaces – a survey of molecular fundamentals, resulting effects and novel preventive strategies in CE
Authors: Stutz Hanno
Published: July 2009

This review addresses the fundamentals governing the adsorption of individual protein molecules onto the surface of fused‐silica capillaries, the protein aggregation to adsorbate clusters and their final accretion to monolayers with subsequent stratification to protein multilayers. The attention in CE protein separation has primarily been focused on (i) tuning the BGE including the buffer type, ionic strength, pH and additives, (ii) tailored post‐rinse procedures to detach adhered protein residues and (iii) the optimization of capillary wall shielding in order to reduce protein attachment. Improvements in protein separation as well as related adverse effects are mainly discussed on the basis of parameters known to become deteriorated in case of protein adhesion, e.g. repeatability of the EOF and of migration times, peak width, theoretical plate numbers, resolution and asymmetry factor. However, knowledge of the molecular principles controlling protein adsorption onto silica surfaces is indispensable for separation optimization. Furthermore, it facilitates troubleshooting and the interpretation of undesired concomitant phenomena. This review comprehensively discusses protein adsorption models derived from surface chemistry primarily in terms of their relevance for CE, clearly showing that the adsorption process in its complexity is only partially revealed by models, which address single or binary protein solutions. In a further section theoretical concepts and surface models are related to surface phenomena encountered in CE. The final part of the review surveys recent concepts for prevention of protein adhesion, thereby addressing capillary treatment, favorable buffer types, dynamic and adhesive semi‐permanent coating strategies covering the literature from 2000–2008.
Complete sequencing of GABAAreceptor subunit β3 by a rapid technique following in‐gel digestion of the protein
Authors: Kang Sung Ung , Lubec Gert
Published: July 2009

Knowledge on complete sequences is pivotal to identify splice variants, generate specific antibodies and predict conformation. A simple analytical approach to obtain 100% sequence coverage, however, is currently not available. Recombinant gamma‐aminobutyric acid A receptor subunits were from insect SF9 cells that were co‐transfected with rat α1 and His‐tag β3. The complex of these two subunits was run on blue‐native PAGE, followed by multidimensional electrophoretic steps. Spots resolved at the third electrophoretic step were in‐gel digested with trypsin, chymotrypsin and Asp‐N. In‐gel modification of lysines by acetylation was carried out to increase sequence coverage. Subsequently, peptides were analyzed by nano‐ESI‐LC‐MS/MS using both, collision‐induced dissociation and electron transfer dissociation principles. When results from trypsin, chymotrypsin and Asp‐N digestion were combined, a single peptide [424 KKTHLRRRSSQL 435] was still not identified. In‐gel lysine acetylation leads to unambiguous identification of this peptide by the use of MASCOT v2.2. The use of the Modiro™software along with MASCOT, however, was able to provide 100% sequence coverage even without the use of in‐gel lysine acetylation. It was observed that the use of trypsin, chymotrypsin and Asp‐N with bioinformatic handling by the MASCOT and Modiro™software is sufficient to obtain complete sequencing of a highly hydrophobic membrane protein.
Simple method for determination of cocaine and main metabolites in urine by CE coupled to MS
Authors: da Costa José Luiz , Tonin Fernando Gustavo , Zanolli Luiz Antonio , da Matta Chasin Alice Aparecida , Tavares Marina Franco Maggi
Published: July 2009

In this work, a simple method for the simultaneous determination of cocaine (COC) and five COC metabolites (benzoylecgonine, cocaethylene (CET), anhydroecgonine, anhydroecgonine methyl ester and ecgonine methyl ester) in human urine using CE coupled to MS via electrospray ionization (CE‐ESI‐MS) was developed and validated. Formic acid at 1 mol/L concentration was used as electrolyte whereas formic acid at 0.05 mol/L concentration in 1:1 methanol:water composed the coaxial sheath liquid at the ESI nozzle. The developed method presented good linearity in the dynamic range from 250 ng/mL to 5000 ng/mL (coefficient of determination greater than 0.98 for all compounds). LODs (signal‐to‐noise ratio of 3) were 100 ng/mL for COC and CET and 250 ng/mL for the other studied metabolites whereas LOQ's (signal‐to‐noise ratio of 10) were 250 ng/mL for COC and CET and 500 ng/mL for all other compounds. Intra‐day precision and recovery tests estimated at three different concentration levels (500, 1500 and 5000 ng/mL) provided RSD lower than 10% (except anhydroecgonine, 18% RSD) and recoveries from 83–109% for all analytes. The method was successfully applied to real cases. For the positive urine samples, the presence of COC and its metabolites was further confirmed by MS/MS experiments.
Fabrication of a microfluidic enzyme reactor utilizing magnetic beads
Authors: Liu Xiaojun , Lo Roger C. , Gomez Frank A.
Published: July 2009

An enzyme‐catalyzed microfluidic assay using magnetic micro‐beads is described. Here, diaphorase (DI) (E.C. 1.6.99) is covalently attached to the magnetic micro‐beads (2.7 μm) and integrated into a short section of a microchip fabricated from PDMS. DI converts non‐fluorescent resazurin to fluorescent resorufin in the presence of nicotinamide adenine dinucleotide phosphate (NADH). In this work, an embedded magnet holds the micro‐beads in place within the microchannel while a solution of resazurin and NADH in buffer is flowed through the beads. Incorporation of the micro‐beads into the microchannel requires only a few minutes and offers well‐defined spatial resolution and reproducibility. At a flow rate of 41.2 μL/h, a stable state for the enzyme reaction in the microfluidic format was achieved within 50 s. The maximum conversion of the reaction was obtained at a concentration of 1.25 mM NADH. The reaction yield is affected by ZnCl2 and at concentrations in excess of 90.0 mM, the activity of DI was almost double without ZnCl2. At 5.2 mM potassium chloride, the activity of DI reached its maximum value. Overall, the conversion of resazurin in microfluidic format was more than twice than that in a batch assay.
Introducing the CPL/MUW proteome database: Interpretation of human liver and liver cancer proteome profiles by referring to isolated primary cells
Authors: Wimmer Helge , Gundacker Nina C. , Griss Johannes , Haudek Verena J. , Stättner Stefan , Mohr Thomas , Zwickl Hannes , Paulitschke Verena , Baron David M. , Trittner Wolfgang , Kubicek Markus , Bayer Editha , Slany Astrid , Gerner Christopher
Published: July 2009

Interpretation of proteome data with a focus on biomarker discovery largely relies on comparative proteome analyses. Here, we introduce a database‐assisted interpretation strategy based on proteome profiles of primary cells. Both 2‐D‐PAGE and shotgun proteomics are applied. We obtain high data concordance with these two different techniques. When applying mass analysis of tryptic spot digests from 2‐D gels of cytoplasmic fractions, we typically identify several hundred proteins. Using the same protein fractions, we usually identify more than thousand proteins by shotgun proteomics. The data consistency obtained when comparing these independent data sets exceeds 99% of the proteins identified in the 2‐D gels. Many characteristic differences in protein expression of different cells can thus be independently confirmed. Our self‐designed SQL database (CPL/MUW – database of the Clinical Proteomics Laboratories at the Medical University of Vienna accessible via www.meduniwien.ac.at/proteomics/database) facilitates (i) quality management of protein identification data, which are based on MS, (ii) the detection of cell type‐specific proteins and (iii) of molecular signatures of specific functional cell states. Here, we demonstrate, how the interpretation of proteome profiles obtained from human liver tissue and hepatocellular carcinoma tissue is assisted by the Clinical Proteomics Laboratories at the Medical University of Vienna‐database. Therefore, we suggest that the use of reference experiments supported by a tailored database may substantially facilitate data interpretation of proteome profiling experiments.
Nanostructured pillars based on vertically aligned carbon nanotubes as the stationary phase in micro‐CEC
Authors: Wu Ren‐Guei , Yang Chung‐Shi , Wang Pen‐Cheng , Tseng Fan‐Gang
Published: July 2009

We present a micro‐CEC chip carrying out a highly efficient separation of dsDNA fragments through vertically aligned multi‐wall carbon nanotubes (MWCNTs) in a microchannel. The vertically aligned MWCNTs were grown directly in the microchannel to form straight nanopillar arrays as ordered and directional chromatographic supports. 1‐Pyrenedodecanoic acid was employed for the surface modification of the MWCNTs' stationary phase to adsorb analytes by hydrophobic interactions. This device was used for separating dsDNA fragments of three different lengths (254, 360, and 572 bp), and fluorescence detection was employed to verify the electrokinetic transport in the MWCNT array. The micro‐CEC separation of the three compounds was achieved in less than 300 s at a field strength of 66 V/cm due to superior laminar flow patterns and a lower flow resistance resulting from the vertically aligned MWCNTs being used as the stationary phase medium. In addition, a fivefold reduction of band broadening was obtained when the analyte was separated by the chromatographic MWCNT array channel instead of the CE channel. From all of the results, we suggest that an in situ grown and directional MWCNT array can potentially be useful for preparing more diversified forms of stationary phases for vertically efficient chip‐based electrochromatography.
Visualizing disease associations: graphic analysis of frequency distributions as a function of age using moving average plots (MAP) with application to Alzheimer's and Parkinson's disease
Authors: Payami Haydeh , Kay Denise M. , Zabetian Cyrus P. , Schellenberg Gerard D. , Factor Stewart A. , McCulloch Colin C.
Published: July 2009

Age‐related variation in marker frequency can be a confounder in association studies, leading to both false‐positive and false‐negative findings and subsequently to inconsistent reproducibility. We have developed a simple method, based on a novel extension of moving average plots (MAP), which allows investigators to inspect the frequency data for hidden age‐related variations. MAP uses the standard case‐control association data and generates a birds‐eye view of the frequency distributions across the age spectrum; a picture in which one can see if, how, and when the marker frequencies in cases differ from that in controls. The marker can be specified as an allele, genotype, haplotype, or environmental factor; and age can be age‐at‐onset, age when subject was last known to be unaffected, or duration of exposure. Signature patterns that emerge can help distinguish true disease associations from spurious associations due to age effects, age‐varying associations from associations that are uniform across all ages, and associations with risk from associations with age‐at‐onset. Utility of MAP is illustrated by application to genetic and epidemiological association data for Alzheimer's and Parkinson's disease. MAP is intended as a descriptive method, to complement standard statistical techniques. Although originally developed for age patterns, MAP is equally useful for visualizing any quantitative trait. Genet. Epidemiol. 34:92–99, 2010. © 2009 Wiley‐Liss, Inc.
Methods for detecting interactions between genetic polymorphisms and prenatal environment exposure with a mother‐child design
Authors: Wang Shuang , Zheng Tian , Chanock Stephen , Jedrychowski Wieslaw , Perera Frederica P.
Published: July 2009

Prenatal exposures such as polycyclic aromatic hydrocarbons and early postnatal environmental exposures are of particular concern because of the heightened susceptibility of the fetus and infant to diverse environmental pollutants. Marked inter‐individual variation in response to the same level of exposure was observed in both mothers and their newborns, indicating that susceptibility might be due to genetic factors. With the mother‐child pair design, existing methods developed for parent‐child trio data or random sample data are either not applicable or not designed to optimally use the information. To take full advantage of this unique design, which provides partial information on genetic transmission and has both maternal and newborn outcome status collected, we developed a likelihood‐based method that uses both the maternal and the newborn information together and jointly models gene‐environment interactions on maternal and newborn outcomes. Through intensive simulation studies, the proposed method has demonstrated much improved power in detecting gene‐environment interactions. The application on a real mother‐child pair data from a study conducted in Krakow, Poland, suggested four significant gene‐environment interactions after multiple comparisons adjustment. Genet. Epidemiol. 34: 125–132, 2010. © 2009 Wiley‐Liss, Inc.
Quality of life analysis in patients with anterior skull base neoplasms
Authors: Palme Carsten E. , Irish Jonathan C. , Gullane Patrick J. , Katz Mark R. , Devins Gerald M. , Bachar Gideon
Published: July 2009

Background.

Significant morbidity is associated with management of anterior skull base neoplasms. The aim of this study was to evaluate the posttreatment patient's quality of life (QOL).

Methods.

A retrospective chart review identified 27 patients. QOL tools included the Functional Assessment of Cancer Therapy–Head & Neck, Centre for Epidemiologic Studies Depression Scale (CES‐D), Atkinson Life Happiness Rating (ALHR), and Midface Dysfunction Scale (MDS).

Results.

Postoperative radiotherapy and chemotherapy was required in 16 and 2 patients, respectively. The median FACT, ALHR, and CES‐D scores were 118 ± 21, 9 ± 2, and 17 ± 8, respectively. Smell and nasal crusting disturbance was reported by 69% and 61%, respectively. CES‐D > 16 and patients with recurrent disease correlated with a lower Total‐FACT score. Adjuvant radiotherapy correlated with a lower FACT‐H&N score. Patient sex, marital‐status, pathology, surgical technique, or complication rate did not correlate with worse QOL.

Conclusion.

Anterior skull base neoplasms survivors have an overall acceptable QOL. Most complaints relate to MDS. Recurrence, adjuvant radiotherapy, and MDS had lower QOL scores. © 2009 Wiley Periodicals, Inc. Head Neck, 2009
Spurious hypercalcitoninemia in patients with nodular thyroid disease induced by heterophilic antibodies
Authors: Kim Jung Min , Chung Ki‐Wook , Kim Seok Won , Choi Seon Hyeong , Min Hye Sook , Kim Ji‐na , Won Woo‐jae , Kim Seok Ki , Lee Ji In , Chung Jae Hoon , Kim Sun Wook
Published: July 2009

Background

Serum calcitonin is the most useful tumor marker for the diagnosis and follow‐up of medullary thyroid carcinoma (MTC). Spurious hypercalcitoninemia caused by heterophilic antibody interference (HAI) is rarely found in patients without MTC.

Methods

We studied 2 patients with hypercalcitoninemia and thyroid nodules, but no evidence of MTC on fine‐needle aspiration cytology. We performed calcium stimulation tests, measured serum calcitonin with another calcitonin kit, performed dilution tests, and remeasured serum calcitonin after applying heterophilic blocking tubes.

Results

In a 31‐year‐old woman with no response to the calcium stimulation test, serum calcitonin was <5 pg/mL using another kit. After we applied heterophilic blocking tubes, the serum calcitonin level decreased to normal range. We concluded that patient had spurious hypercalcitoninemia. In a 63‐year‐old woman, all tests revealed that the patient had true hypercalcitoninemia. The patient underwent total thyroidectomy that revealed MTC.

Conclusions

We suggest that patients suspected for spurious hypercalcitoninemia should undergo further investigation due to HAI. © 2009 Wiley Periodicals, Inc. Head Neck, 2010
Frequent expression of Niban in head and neck squamous cell carcinoma and squamous dysplasia
Authors: Ito Shin , Fujii Hiroaki , Matsumoto Toshiharu , Abe Masaaki , Ikeda Katsuhisa , Hino Okio
Published: July 2009

Background

Niban was initially identified in the Eker rat, a model of renal carcinogenesis. We examined Niban expression in head and neck squamous cell carcinoma (HNSCC) and head and neck dysplastic lesions.

Methods

Using a polyclonal rabbit anti‐human Niban antibody, 43 cases of HNSCC and 30 cases of head and neck squamous dysplasia were immuonohistochemically stained for Niban. Ancillary genetic studies were also performed.

Results

Forty‐two of 43 HNSCCs (97.6%) and 20 of 30 (66.6%) dysplastic lesions were positively stained for Niban. The staining was generally less intense in cases of dysplasia than HNSCC. Three of 8 normal mucosal samples from drinker/smokers also showed weak Niban expression. Normal head and neck squamous epithelium from nondrinker/nonsmokers did not stained for Niban. Reverse transcription polymerase chain reaction results matched the immuonohistochemical results.

Conclusion

The expression of Niban frequently begins in the early stages of head and neck squamous carcinoma and remains upregulated throughout the carcinogenic process. Niban may be a good molecular marker of HNSCC. © 2009 Wiley Periodicals, Inc. Head Neck, 2010
Importance of comorbidity in hypopharyngeal cancer
Authors: Homma Akihiro , Sakashita Tomohiro , Oridate Nobuhiko , Suzuki Fumiyuki , Suzuki Seigo , Hatakeyama Hiromitsu , Mizumachi Takatsugu , Taki Shigenari , Fukuda Satoshi
Published: July 2009

Background.

Comorbidity has an impact on survival in laryngeal cancer in several reports. However, the importance of comorbidity in hypopharyngeal cancer (HPC) has not been reported.

Methods.

A retrospective medical record review of 156 patients with HPC treated between 1995 and 2005 was performed. Comorbid illness was measured by the Adult Comorbidity Evaluation‐27. A Cox proportional hazards model was used to determine the factors related to overall survival.

Results.

Comorbidity was absent in 55 (35.2%) of the patients, mild in 39 (25%), moderate in 28 (17.9%), and severe in 34 (21.8%). There were statistically significant differences between the survival rates in accord with age, stage, subsite, and comorbidity (45.1% for none or mild vs 27.7% for moderate or severe; p = .0073). Age, stage, and comorbidity were identified as independent prognostic factors in the multivariate analysis.

Conclusion.

Comorbidity, along with the clinical stage, should be considered in treatment planning for patients with HPC. © 2009 Wiley Periodicals, Inc. Head Neck, 2010
Primary schwannoma in a cervical lymph node
Authors: Black Jennifer O. , Zhai Qihui Jim , Varona Orlando B. , Ordonez Nelson G. , Luna Mario A.
Published: July 2009

Background.

Spindle cell neoplasms within lymph nodes are rare and include benign and malignant tumors and primary and metastatic tumors such as palisaded myofibroblastoma, leiomyoma, leiomyosarcoma, reticular cell neoplasms, and vascular sarcomas. Ancillary studies may help distinguish these neoplasms.

Methods.

A 77‐year‐old white woman was seen with a painless, slowly growing mass of the left neck. Her clinical history was noncontributory. An excisional biopsy was performed without complication. There has been no recurrence, to date, of the lesion.

Results.

Gross examination, microscopic examination, immunohistochemistry, and ultrastructural studies were consistent with the diagnosis of schwannoma arising within a lymph node.

Conclusions.

We report the first case of intranodal schwannoma arising in a cervical lymph node. The recognition of intranodal schwannoma is important because it is cured with excision, whereas some of the other diagnostic considerations for a spindle cell lesion within a lymph node may require radiation or chemotherapy. © 2009 Wiley Periodicals, Inc. Head Neck, 2009
Severe radiation therapy–related soft tissue toxicity in a patient with porphyria cutanea tarda: A literature review
Authors: Gunn G. Brandon , Anderson Karl E. , Patel Abhilasha J. , Gallegos Juan , Hallberg Csilla Kormos , Sood Gagan , Hatch Sandra S. , Sanguineti Giuseppe
Published: July 2009

Background.

Some porphyrias are associated with cutaneous phototoxicity due to photoactivation of porphyrins, but whether ionizing radiation can have an additive effect is not clear. We report a case of severe radiation therapy‐related toxicity in a patient with porphyria cutanea tarda and review the literature.

Methods.

A 50‐year‐old man with porphyria cutanea was treated for lower lip squamous cell carcinoma with definitive radiation therapy. During radiation therapy, acute toxicity was of an expected onset and severity. Six months after treatment completion, he developed skin hypopigmentation, soft tissue fibrosis, and areas of painful denuded skin and crusting within the previous treatment field.

Results.

Reports of 7 patients with porphyria receiving radiation therapy to at least 9 separate sites were reviewed, with only 1 previous report suggestive of increased radiation therapy–related toxicity.

Conclusion.

Based on this and 1 other report, caution is warranted when considering radiation therapy in patients with active porphyria. © 2009 Wiley Periodicals, Inc. Head Neck, 2009
Neuroendocrine neoplasms of the larynx: An overview
Authors: Ferlito Alfio , Silver Carl E. , Bradford Carol R. , Rinaldo Alessandra
Published: July 2009

Neuroendocrine neoplasms of the larynx are rare but are the most common nonsquamous tumors of this organ. In the past, there has been considerable confusion about the nature and classification of these neoplasms, but the current consensus is that there are 4 different types of laryngeal neuroendocrine tumors composed of paraganglioma, typical carcinoid, atypical carcinoid tumor, and small cell neuroendocrine carcinoma. Carcinoids and small cell neuroendocrine carcinomas are epithelial neoplasms, whereas paragangliomas are of neural origin. Diagnosis is based primarily on light microscopy and confirmed by immunohistochemistry and electron microscopy. Precise diagnosis is essential because the natural history, treatment, and prognosis vary widely for the different neoplastic categories.

Typical carcinoids are very rare and are treated by wide local excision, usually partial laryngectomy, without elective neck dissection. Atypical carcinoid tumors are more common and more aggressive. They are treated by partial or total laryngectomy with elective or therapeutic neck dissection. Adjuvant chemo/radiotherapy may be of benefit in some cases. Small cell neuroendocrine carcinomas are highly aggressive and should be considered disseminated at initial diagnosis. The treatment is by irradiation and chemotherapy as surgery has proven to be of a little benefit. Paragangliomas are treated by local excision or partial laryngectomy.

It is difficult to determine the valid survival statistics for typical carcinoids because of their rarity and confusion in the literature with their atypical counterparts. They have a greater tendency to metastasize, and thus a worse prognosis than was previously believed. Atypical carcinoid tumors have a 5‐year survival rate of approximately 50%, which decreases with time. The prognosis of small cell neuroendocrine carcinoma of the larynx is dismal, with 5‐year survival rates of 5%. The biological behavior of laryngeal paraganglioma is generally benign and the prognosis is excellent. © 2009 Wiley Periodicals, Inc. Head Neck, 2009
Feasibility of standard mechanical ventilation with low FiO2 and small endotracheal tubes during laser microlaryngeal surgery
Authors: Nicelli Elisa , Gemma Marco , De Vitis Assunta , Foti Giuseppe , Beretta Luigi
Published: July 2009

Background.

No technique can be considered as a gold standard for ventilation during direct laser CO2 laryngeal microsurgery. We evaluated the feasibility of standard ventilation with laser‐safe endotracheal tubes (ETTs) and inspired O2 fraction (FiO2) = 0.21 during direct microlaryngoscopy.

Methods.

During total intravenous anesthesia, standard mechanical normoventilation was set with FiO2 = 0.21 and 50 mm Hg peak inspiratory pressure limit. If SpO2 was <90% for >2 minutes, FiO2 was increased to 0.3; after 4 minutes it was increased to 0.4; after another 4 minutes, positive end‐expiratory pressure (PEEP) could be set at 5 cm H2O; and after another 4 minutes, surgery was stopped if SpO2 remained <90%.

Results.

We studied 111 consecutive direct microlaryngoscopies on different patients. Four patients (3.6%) suffered minor intraoperative desaturation. Barotrauma was not observed, PEEP was never applied, and surgery was never stopped. Body mass index was independently predictive of the occurrence of intraoperative desaturation.

Conclusions.

Standard mechanical ventilation with FiO2 = 0.21 through laser‐safe ETTs is feasible during direct microlaryngoscopy. © 2009 Wiley Periodicals, Inc. Head Neck, 2010
Balancing the funds in the New Cooperative Medical Scheme in rural China: determinants and influencing factors in two provinces
Authors: Zhang Luying , Cheng Xiaoming , Liu Xiaoyun , Zhu Kun , Tang Shenglan , Bogg Lennart , Dobberschuetz Karin , Tolhurst Rachel
Published: July 2009

In recent years, the central government in China has been leading the re‐establishment of its rural health insurance system, but local government institutions have considerable flexibility in the specific design and management of schemes. Maintaining a reasonable balance of funds is critical to ensure that the schemes are sustainable and effective in offering financial protection to members. This paper explores the financial management of the NCMS in China through a case study of the balance of funds and the factors influencing this, in six counties in two Chinese provinces. The main data source is NCMS management data from each county from 2003 to 2005, supplemented by: a household questionnaire survey, qualitative interviews and focus group discussions with all local stakeholders and policy document analysis. The study found that five out of six counties held a large fund surplus, whilst enrolees obtained only partial financial protection. However, in one county greater risk pooling for enrolees was accompanied by relatively high utilisation levels, resulting in a fund deficit. The opportunities to sustainably increase the financial protection offered to NCMS enrolees are limited by the financial pressures on local government, specific political incentives and low technical capacities at the county level and below. Our analysis suggests that in the short term, efforts should be made to improve the management of the current NCMS design, which should be supported through capacity building for NCMS offices. However, further medium‐term initiatives may be required including changes to the design of the schemes. Copyright © 2009 John Wiley & Sons, Ltd.
Parameterizing redistribution and sublimation of blowing snow for hydrological models: tests in a mountainous subarctic catchment
Authors: MacDonald Matthew K. , Pomeroy John W. , Pietroniro Alain
Published: July 2009

Model tests of blowing snow redistribution and sublimation by wind were performed for three winters over a small mountainous sub‐Arctic catchment located in the Yukon Territory, Canada, using a physically based blowing snow model. Snow transport fluxes were distributed over multiple hydrological response units (HRUs) using inter‐HRU snow redistribution allocation factors (SR). Three SR schemes of varying complexity were evaluated. Model results show that end‐of‐winter snow accumulation can be most accurately simulated using a physically based blowing snow model when SR values are established when taking into account wind direction and speed and HRU aerodynamic characteristics, along with the spatial arrangement of the HRUs in the catchment. With the knowledge that snow transport scales approximately with the fourth power of wind speed (u4), SR values can be (1) established according to the predominant u4 direction and magnitude over a simulation period or (2) can change at each time step according to a measured wind direction. Unfortunately, wind direction data were available only for one of the three winters, so the latter scheme was tested only once. Although the aforementioned SR schemes produced different results, model efficiency was of similar merit. The independent effects of topography and vegetation were examined to assess their importance on snow redistribution modelling over mountainous terrain. Snow accumulation was best simulated when including explicit representations of both landscape vegetation (i.e. vegetation height and density) and topography (i.e. wind exposure). There may be inter‐basin differences in the relative importance of model representations of topography and vegetation. Copyright © 2009 John Wiley & Sons, Ltd.
Body mass index and mortality from lung cancer in smokers and nonsmokers: A nationally representative prospective study of 220,000 men in China
Authors: Yang Ling , Yang Gonghuan , Zhou Maigeng , Smith Margaret , Ge Hui , Boreham Jillian , Hu Yisong , Peto Richard , Wang Jun , Chen Zhengming
Published: July 2009

Low body mass index (BMI) has been associated with increased risk of lung cancer. However, the nature of the association, especially in populations with relatively low BMI, is less well characterized, as is the relevance to it of smoking. A nationally representative prospective cohort study included 217,180 Chinese men aged 40–79 years in 1990–91 who had no prior history of cancer and were followed up for 15 years. Standardized hazard ratios (HRs) were calculated for lung cancer mortality by baseline BMI. The mean baseline BMI was 21.7 kg/m2, and 2,145 lung cancer deaths were recorded during 15 years of follow‐up. The prevalence of smoking was strongly inversely associated with BMI, but no apparent relationship was seen between amount smoked (or other measures of smoking intensity) and BMI among smokers. Overall there was a strong inverse association between BMI and lung cancer mortality (p< 0.0001 for trend) after excluding the first 3 years of follow‐up. This association appeared to be confined mainly to current smokers, with no apparent relationship in nonsmokers (p< 0.001 for difference between slopes). Among current smokers, the inverse association appeared to be log‐linear, with each 5 kg/m2lower BMI associated with a 35% (95% confidence interval: 24–46%;p< 0.0001) higher lung cancer mortality, and it persisted after excluding those who had reported poor health status or history of any disease or respiratory symptoms at baseline. In this relatively lean Chinese male population, low BMI was strongly associated with increased risk of lung cancer only among current smokers. © 2009 UICC