bluuebunny/crossref_metadata_2025 huggingface dataset:
Ionic channels and neuropathic pain: Phisiopatology and applications
Authors: Aurilio Caterina , Pota Vincenzo , Pace Maria Caterina , Passavanti Maria Beatrice , Barbarisi Manlio
Published: January 2008

Neuropathic pain is defined by the International Association for Pain research as a pain associated to a primary lesion or a dysfunction of the central or peripheral system. Over the past few years the causes of the neuropathic pain were not known and there were not good treatments for it, now we have a better knowledge of the physiopathological aspects and there is a wider diffusion of the research for target aimed therapies. The physiologic genesis of nervous messages occurs exclusively in skin sensorial endings or in nerve tissues as a consequence of an adequate sensorial stimulus and depends on the quick variations of the electric potential difference at the endings of ionic membranes. These variations of even 500 V a second are possible because of the presence of ionic channels. In neuropathic pain impulses can be originated even from ectopic sites. Ectopic discharges originated in a peripheral neuropathic system have an important role in the early stage of neuropathic pain development in two different ways. First they give an excess of spontaneous and evoked electric impulses to the central nervous system, causing a primitive neuropathic pain signal; then the ectopic activity develops and maintains the central sensitisation process. All this amplifies the afferent signals deriving from residual efferents that go on innerving cutaneous areas damaged and partly disnerved, causing tactile allodynie. Sodium channels are the greatest responsible for electrogenesis, that is the basis of the action potential generation and its propagation. Action potential begins after a depolarization such that it could cause a membrane transitory modification, turning prevalently permeable to Na+ more than to K+ as during a release phase. Neuropathy generates a local accumulation of sodium channels, with a consequent increase of density. This remodel seems to be the basis of neuro hyperexecitably. Calcium channels have also an important role in cell working. Intracellular calcium increase contributes to depolarization processes, through kinase and determines the phosphorylation of membrane proteins that can make powerful the efficacy of the channels themselves. In the future new diagnostic opportunities of physiopathologist mechanism leading to neuropathic pain will allow treatments aimed at specific molecular changes of ionic channels. J. Cell. Physiol. 215: 8–14, 2008. © 2008 Wiley‐Liss, Inc.
Fracture induced mobilization and incorporation of bone marrow‐derived endothelial progenitor cells for bone healing
Authors: Matsumoto Tomoyuki , Mifune Yutaka , Kawamoto Atsuhiko , Kuroda Ryosuke , Shoji Taro , Iwasaki Hiroto , Suzuki Takahiro , Oyamada Akira , Horii Miki , Yokoyama Ayumi , Nishimura Hiromi , Lee Sang Yang , Miwa Masahiko , Doita Minoru , Kurosaka Masahiro , Asahara Takayuki
Published: January 2008

We recently reported that systemic administration of peripheral blood (PB) CD34+ cells, an endothelial progenitor cell (EPC)‐enriched population, contributed to fracture healing via vasculogenesis/angiogenesis. However, pathophysiological role of EPCs in fracture healing process has not been fully clarified. Therefore, we investigated the hypothesis whether mobilization and incorporation of bone marrow (BM)‐derived EPCs may play a pivotal role in appropriate fracture healing. Serial examinations of Laser doppler perfusion imaging and histological capillary density revealed that neovascularization activity at the fracture site peaked at day 7 post‐fracture, the early phase of endochondral ossifification. Fluorescence‐activated cell sorting (FACS) analysis demonstrated that the frequency of BM cKit+Sca1+Lineage− (Lin−) cells and PB Sca1+Lin− cells, which are EPC‐enriched fractions, significantly increased post‐fracture. The Sca1+ EPC‐derived vasuculogenesis at the fracture site was confirmed by double immunohistochemistry for CD31 and Sca1. BM transplantation from transgenic donors expressing LacZ transcriptionally regulated by endothelial cell‐specific Tie‐2 promoter into wild type also provided direct evidence that EPCs contributing to enhanced neovascularization at the fracture site were specifically derived from BM. Animal model of systemic administration of PB Sca1+Lin− Green Fluorescent Protein (GFP)+ cells further confirmed incorporation of the mobilized EPCs into the fracture site for fracture healing. These findings indicate that fracture may induce mobilization of EPCs from BM to PB and recruitment of the mobilized EPCs into fracture sites, thereby augment neovascularization during the process of bone healing. EPCs may play an essential role in fracture healing by promoting a favorable environment through neovascularization in damaged skeletal tissue. J. Cell. Physiol. 215: 234–242, 2008. © 2008 Wiley‐Liss, Inc.
Helicobacter pylori heat shock protein B (HspB) localizes in vivo in the gastric mucosa and MALT lymphoma
Authors: De Luca Antonio , De Falco Maria , Manente Lucrezia , Dattilo Doriana , Lucariello Angela , Esposito Vincenzo , Gnarini Mariarosaria , Citro Gennaro , Baldi Alfonso , Tufano Maria Antonietta , Iaquinto Gaetano
Published: January 2008

Heat shock protein B (HspB) is one of the dominant proteins recognized by most Helicobacter pylori‐infected persons and is being considered as potential candidates for subunit vaccines. In the present study we describe the generation of an antibody against HspB and its use in immunohistochemical assays on gastric biopsies. We have demonstrated that our rabbit polyclonal antibody against HspB did not recognize any protein in lysates from a lung human epithelial cell (H1299) line and did not cross‐react with the other members of human heat shock proteins. Secondly, we have observed that in gastric biopsies, HspB immunostaining was present inside the cytoplasm of human epithelial cells with a particular localization in the apical portion of gastric epithelial cells other than in the extracellular spaces among gastric cells of human stomach. Finally, we have demonstrated a cytoplasmic HspB immunostaining in groups of neoplastic cells of MALT lymphoma. In conclusion, our observations suggest a possible involvement of HspB in the pathogenesis of H. pylori‐related pathologies such as gastritis, ulcer and gastric cancer. J. Cell. Physiol. 216: 78–82, 2008. © 2008 Wiley‐Liss, Inc.
PACAP provides colonic protection against dextran sodium sulfate induced colitis
Authors: Azuma Yasu‐Taka , Hagi Kiyomi , Shintani Norihito , Kuwamura Mitsuru , Nakajima Hidemitsu , Hashimoto Hitoshi , Baba Akemichi , Takeuchi Tadayoshi
Published: January 2008

Pituitary adenylate cyclase‐activating polypeptide (PACAP) plays a crucial role in immunity and inflammation. Our aim was to obtain insight in the role of PACAP in experimental colitis in mice and thus its possible role in inflammatory bowel disease. PACAP‐deficient (PACAP−/−) mice and wild‐type control mice were challenged by colitis‐inducing agent, dextran sulfate sodium (DSS). We monitored clinical symptoms, intestinal morphology, and difference of cytokine production in the proximal and distal colon. After DSS administration, mortality was more severe inPACAP−/−mice versus wild‐type control mice. The histological score and the disease activity index ofPACAP−/−mice were significantly higher than those of wild‐type control mice. In proximal colon, production of IL‐1β and IL‐6 inPACAP−/−mice were significantly upregulated on day 8 after DSS administration, compared to wild‐type control mice. In distal colon, furthermore, production of IFNγ, IL‐1β, IL‐6, IL‐12, and KC were significantly higher inPACAP−/−mice than in wild‐type control mice on day 4. Our findings indicate that PACAP regulates the production of pro‐inflammatory cytokine in the experimental colitis. J. Cell. Physiol. 216: 111–119, 2008. © 2008 Wiley‐Liss, Inc.
Comparative stability of perpendicular versus parallel double‐locking plating systems in osteoporotic comminuted distal humerus fractures
Authors: Stoffel Karl , Cunneen Sam , Morgan Robert , Nicholls Rochelle , Stachowiak Gwidon
Published: January 2008

In distal humerus fractures, the restoration of stability is important to allow early mobilization and hence more favorable functional outcomes. In this article, we compare the biomechanical stability of perpendicular and parallel locking plating systems for the internal fixation of AO Type C2 distal humerus fractures in osteoporotic bone. Fractures were simulated in paired cadaveric bones and fixed using either the perpendicular 3.5 mm LCP distal humerus plating system (Synthes; Sydney, Australia) or the parallel Mayo Clinic Congruent elbow plate system (Acumed; Hillsboro, OR), using locking screws in both systems. Both systems were then tested for their stiffness (in compression and internal/external rotation), plastic deformation, and failure in torsion. Comparatively, the parallel locking plate system provided a significantly higher stability in compression (p = 0.005) and external rotation (p = 0.006), and a greater ability (p = 0.005) to resist axial plastic deformation. Stability for both constructs appeared to be dependent on bone quality, however the stability of the perpendicular system was generally more sensitive to bone mineral density, indicating a possible need for additional independent interfragmentary screws. A disadvantage of the parallel locking plate system was wear debris produced by its tapping system. In summary, the biomechanical findings of this study suggest that both locking plate systems allow early mobilization of the elbow in patients with osteoporotic bone following fixation of a comminuted distal humerus fracture. However, the parallel locking system showed improved stability compared with the perpendicular locking system, and therefore may be more indicated. © 2008 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 26:778–784, 2008
Measurement of bone blood flow using the hydrogen washout technique—part II: Validation by comparison to microsphere entrapment
Authors: Larsen Mikko , Pelzer Michael , Friedrich Patricia F. , Bishop Allen T.
Published: January 2008

Accurate and reproducible measurement of bone blood flow has important clinical and experimental applications. Hydrogen washout is simple, safe, and widely used, but its use in bone tissue has not been validated. To this end, we have compared cortical bone blood flow measurements obtained by radioactive‐labeled microsphere entrapment with those from hydrogen washout. Blood flow was measured in tibial cortical bone of 12 New Zealand White rabbits by radioactive microsphere entrapment and by hydrogen washout. Besides a control group (n = 6), four animals were treated with systemic epinephrine (0.8 µg/kg/min) (group 2) and two with nitroprusside (100 µg/kg/min) (group 3). Furthermore, nine femora from seven rats were isolated on their vascular pedicles and repeated bone blood flow measurements were made at each location with the hydrogen washout method to confirm reproducibility of blood flow determinations by hydrogen washout. An average flow of 2.3 ± 2.0 mL/min/100 g was obtained with the microsphere method and 2.0 ± 0.5 mL/min/100 g with the hydrogen washout method. There was a significant correlation and agreement: R2 = 0.97 (p < 0.01). No consistent flow variations were found with systemic vasoactive drug administration. Hydrogen washout provided reproducible results and showed high sensitivity to flow changes. Hydrogen washout is both sensitive and reproducible in measuring bone blood flow. Results agree well with flow values obtained by labeled microsphere entrapment. © 2008 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 26:746–752, 2008
Study of strain and wetting phenomena in porous silicon by Raman scattering
Authors: Ferrara M. A. , Donato M. G. , Sirleto L. , Messina G. , Santangelo S. , Rendina I.
Published: January 2008

In this paper, porous silicon (PS) layers of different porosity and thickness have been investigated by Raman spectroscopy. The estimation of built‐in strain in PS is reported. Moreover, wetting phenomena in PS layers have been also investigated. The results prove a reversible blue shift of Raman spectra of wetted PS layers with respect to unperturbed layers. We ascribe the shift to a compressive stress due to the increased lattice mismatch between the PS layer and the bulk silicon substrate in wetting conditions. Copyright © 2008 John Wiley & Sons, Ltd.
Micro‐Raman characterizations of Pompei'smortars
Authors: Castriota M. , Cosco V. , Barone T. , De Santo G. , Carafa P. , Cazzanelli E.
Published: January 2008

The ancient town of Pompei offers a unique opportunity to study in detail many aspects of the every day life during the Roman early imperial age. The application of micro‐Raman spectroscopy can be of great help in performing a reasonably rapid comparative analysis of the mortars, quite useful to ascertain the degree of uniformity of the technical recipes among the various building firms and the eventual technical evolution in the time; moreover, the individuation of minerals of specific geographical origins can give useful information about the extension of commercial intercourses. An example of a micro‐Raman investigation on building materials is reported in this work, concerning the analysis of the mortars coming from different points of the wall in the ‘The House of the Wedding of Hercules’. Remarkable differences between ancient and modern mortars are found, allowing a discrimination that can be useful in the case of historical building which underwent several restoration works. Copyright © 2008 John Wiley & Sons, Ltd.
Raman and infrared characterization of the vibrational properties of the antimalarial drug artemisinin
Authors: Moroni Laura , Gellini Cristina , Miranda Maurizio Muniz , Salvi Pier Remigio , Foresti Maria Luisa , Innocenti Massimo , Loglio Francesca , Salvietti Emanuele
Published: January 2008

Artemisinin is one of the most powerful new generation antimalarial drugs. The active center is the peroxide group of the caged trioxane heterocycle, which either blocks the free heme released by the Plasmodium falciparum parasite or acts on key proteins causing the parasite death. Both processes involve the activation of the 1,2,4‐trioxanic ring through interaction with the Fe(II)–heme complex. Since considerable effort was made to synthesize antimalarial drugs containing the endoperoxide group, it becomes fundamental to know the structural and dynamical properties of artemisinin. For this reason, Raman and Fourier transform (FT) infrared studies have been undertaken here on the vibrational properties of artemisinin, its derivative artemether and δ‐valerolactone, the latter being the molecule mimicking the lactonic ring of artemisinin. The vibrational data of the three molecules have been analyzed through the comparison with ab initio calculations based on DFT/B3‐LYP/cc‐pVDZ procedures. Modes of artemisinin have been correlated with those of component units. Copyright © 2008 John Wiley & Sons, Ltd.
Free Rotational Diffusion of Rigid Particles with Arbitrary Surface Topography: A Brownian Dynamics Study Using Eulerian Angles
Authors: Evensen Tom Richard , Naess Stine Nalum , Elgsaeter Arnljot
Published: January 2008

Rotational diffusion of rigid bodies is an important topic that has attracted sustained interest for many decades, but most existing studies are limited to particles with simple symmetries. Here, we present a simple Brownian dynamics algorithm that can be used to study the free rotational diffusion of rigid particles with arbitrary surface topography. The main difference between the new algorithm and previous algorithms is how the numerical values of the mobility tensor are calculated. The only parameters in the numerical algorithm that depend on particle shape are the principal values of the particle rotational mobility tensor. These three scalars contain all information about the surface topography that is relevant for the particle rotational diffusion. Because these principal values only need to be pre‐calculated once, the resulting general algorithm is highly efficient. The algorithm is valid for arbitrary mass density distribution throughout the rigid body. In this paper, we use Eulerian angles as the generalized coordinates describing the particle angular orientation.

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Confinement Effect on the Body‐Centered‐Cubic Phase of Diblock Copolymers in Film
Authors: Tan Hongge , Song Qinggong , Yang Shuang , Yan Dadong , Shi An‐Chang
Published: January 2008

In this paper, we study the morphology of diblock copolymers with the body‐centered‐cubic (bcc) phase confined between two flat surfaces. Employing the Landau–Brazovskii mean field theory and the single mode approximation, we obtain three amplitude parameters as functions of temperature, surface field strength, and film thickness. Because of the effect of confinement size and the surface inducement, the morphology of confined diblock copolymers is different from the bulk structure. By controlling confinement size and surface field strength, lamella, undulated lamella, cylinder, and distorted cylinder can be observed in the bcc bulk phase of diblock copolymers. Also, we construct a “phase diagram” of confinement‐induced structures at different surface field strengths. We compare the present theoretical results with the other relevant theoretical results. The predictions about these interesting confinement‐induced structures should be observable in the experiments under suitable conditions.

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Effects of interactions among polyaniline, camphorsulfonic acid and silica on the structure and properties of their conductive hybrids
Authors: Lee Hsun‐Tsing , Wang Chee‐Chan
Published: January 2008

In this work, the effects of interactions among polyaniline (PAn), camphorsulfonic acid (CSA), and silica on the structure and properties of their sol‐gel hybrids are investigated. These interactions were revealed by FTIR, UV–vis spectra, and XRD patterns. The interaction between PAn and CSA raises conductivities of the CSA‐doped PAn/SiO2 (c‐PAn/SiO2) hybrids. Moreover, the hydrogen bonding interaction between c‐PAn and silicic acid (precursor of SiO2) leads to a less degree of three‐dimensional network structure of the SiO2 component in a hybrid with higher PAn content. In addition, because of the interactions among CSA, Pan, and SiO2, the conductive c‐PAn‐rich phase distributes uniformly in the hybrid and thermal resistance of the hybrid is enhanced consequently. Besides, the c‐PAn/SiO2 hybrid with higher SiO2 content exhibits more significant blue‐shift of its polaron band, lower conductivity, and higher thermal resistance. POLYM. ENG. SCI., 2008. © 2008 Society of Plastics Engineers
High‐density polyethylene reinforced with submicron titania particles
Authors: Bondioli Federica , Dorigato Andrea , Fabbri Paola , Messori Massimo , Pegoretti Alessandro
Published: January 2008

Submicron titania particles were prepared by means of two different synthetic procedures in order to obtain different particle size (diameter ranging from 20 to 350 nm), shapes, and morphologies (amorphous or crystalline). Titania particles were surface modified with octadecylsilane in order to improve their compatibility with respect to polymeric matrices. High‐density polyethylene (HDPE)–titania composites were prepared by melt blending by using an internal mixer. The obtained composites were mechanically characterized in quasi static and creep tensile conditions. The presence of submicron titania particles (1 %vol) led to a significant increase of elastic modulus (20–25%) with respect to the unreinforced HDPE together with a slight increase of yield stress and a decrease of ultimate elongation. An interesting reduction for both elastic and viscoelastic creep compliance components was also evidenced. POLYM. ENG. SCI., 2008. © 2008 Society of Plastics Engineers
Anomalous mechanical behavior upon recycling of poly(phenylene‐ether)‐based thermoplastic elastomer
Authors: Gupta Samik , Pallavi M.B. , Som Abhijit , Krishnamurthy Raja , Bhowmick Anil K.
Published: January 2008

Recycling of thermoplastic elastomers based on poly (phenylene ether) (PPE) was studied in detail. The quaternary blend comprising of styrene–ethylene–butylene–styrene (SEBS)/ethylene vinyl acetate (EVA)/PPE‐PS (polystyrene) showed improvement in mechanical properties upon recycling, which was correlated with the formation of crosslinked network in the system. Presence of crosslinked network was confirmed by the gel content analysis. The blend components involved in the crosslinking were evaluated by gel morphology analysis. Fourier transform infrared spectroscopy revealed the chemical composition of the crosslinked gel. Crosslinking mechanism was established based on the reactivity of allylic EVA radical during recycling. Rheological study supported the notion of crosslinking upon recycling that resulted in higher storage modulus (G′) as a manifestation of restrained flow by network formation. On the basis of the earlier data, a reaction mechanism for crosslinking was proposed. Finally, structure–property correlation was developed through morphological, chemical, and rheological analysis to understand the anomalous enhancement in mechanical properties upon recycling. POLYM. ENG. SCI., 2008. © 2008 Society of Plastics Engineers
The structure‐property relationship of novolac cured epoxy resin/clay nanocomposites
Authors: Tsai Tsung‐Yen , Lu Shau‐Tai , Huang Chin‐Jei , Liu Jia‐Xiang , Li Chih‐Hung , Chen Li‐Chun , Ray Umasankar
Published: January 2008

Intercalated or exfoliated novolac cured epoxy resin nanocomposites were prepared with two different kinds of layered silicates – montmorillonite (PK‐802) and nontronite (PK‐805). The bifunctional modifiers (PI/BEN or MI/BEN) are used to modify the clays for improvement of the properties of polymer where benzalkonium chloride (BEN) acts as a compatibilizing agent and 2‐phenylimidazole (PI) or 2‐methylimidazole (MI) as the accelerators. Both the compatibilizer and accelerator are simultaneously intercalated into the gallery space of pure clays to form the modified clay. The novolac cured epoxy nanocomposites are prepared with these modified clays by crosslinking polymerization reaction. The properties of novolac cured epoxy/clay nanocomposites were characterized by wide‐angle X‐ray diffraction (WAXD), thermo‐gravimetric analysis (TGA), dynamic mechanical analysis (DMA), and transmission electron microscopy (TEM) methods. According to the measurement, these novolac cured epoxy‐clay nanocomposites have been shown the significant improvement in the thermal, mechanical, and barrier properties that may be applied to make printed circuit board. POLYM. ENG. SCI., 2008. © 2008 Society of Plastics Engineers
Styrene/substituted styrene copolymerization by Ph2Zn–metallocene–MAO systems: homo‐ and copolymerization of p‐methoxystyrene with styrene
Authors: Rabagliati Franco M , Mardones Gabriela V , Muñoz Héctor E , Rodríguez Francisco J
Published: January 2008

BACKGROUND: The present work is part of a general study regarding the homo‐ and copolymerization of styrene using diphenylzinc–additive initiator systems, with the aim of improving the properties of commercial atactic polystyrene. The study is focused on syndiotactic polystyrene and/or copolymers of styrene (S) with substituted styrene, styrene derivatives or various α‐olefins. This research has been ongoing over the last 15 years.

RESULTS: The reported experiments show that binary metallocene–methylaluminoxane (MAO) and ternary Ph2Zn–metallocene–MAO, depending on the metallocene employed, are capable of inducing both homo‐ and copolymerization of styrene and p‐methoxystyrene (p‐MeOS). The results indicate that for a styrene/p‐MeOS mole ratio with p‐MeOS > 25% the product obtained has only a minor incorporation of styrene units. The efficiency of the metallocenes studied follows the order bis(n‐butylcyclopentadienyl)titanium dichloride ((n‐BuCp)2TiCl2) > indenyltitanium trichloride (IndTiCl3) > Cp2TiCl2.

CONCLUSION: Metallocenes (n‐BuCp)2TiCl2, Cp2TiCl2 and IndTiCl3 in binary systems combined with MAO, as well as in ternary systems combined with Ph2Zn and MAO, induce the homopolymerization of p‐MeOS and its copolymerization with styrene. The styrene/p‐MeOS copolymer obtained was enriched in p‐MeOS with respect to the initial feed, in agreement with the I+ inductive effect of the methoxy group in the para position of styrene. As already reported, the role of Ph2Zn was nullified by its complexation with the p‐MeOS comonomer. Copyright © 2008 Society of Chemical Industry
The use of biodiesel as a green polymerization solvent at elevated temperatures
Authors: Salehpour Somaieh , Dubé Marc A
Published: January 2008

BACKGROUND: Many important polymers are produced via solution polymerization. The solvent maintains a low viscosity, which provides many practical advantages related to heat transfer, mixing and material handling. Despite these advantages, commonly used solvents often present health and environmental problems. In an effort to replace these toxic solvents, a ‘green’ polymerization solvent, namely canola‐based FAME (fatty acid methyl ester or biodiesel), was used for solution polymerizations at an elevated temperature.

RESULTS: Homopolymerizations of methyl methacrylate, styrene, butyl acrylate and vinyl acetate in FAME were studied at different solvent concentrations at 120 °C. Chain transfer to solvent rate constants (Cfs) were obtained for each polymer system and Arrhenius parameters for Cfs, i.e. Ea and A, were also calculated. These new solvent data were employed in a polymerization simulator to predict rate of polymerization and number‐ and weight‐average molecular weights for these commercially important systems. Model predictions showed reasonable agreement with experimental data.

CONCLUSION: FAME fulfills the demands as a polymerization solvent. From an ecological perspective, FAME provides an environmentally friendly alternative to common solvents. From an industrial perspective, using FAME as a high‐boiling polymerization solvent can increase productivity by enabling polymerizations at elevated temperatures. Copyright © 2008 Society of Chemical Industry
Proteomic analyses of intermediate filaments reveals cytokeratin8 is highly acetylated – implications for colorectal epithelial homeostasis
Authors: Leech Siân H. , Evans Caroline A. , Shaw Leila , Wong Chi H. , Connolly Joanne , Griffiths John R. , Whetton Anthony D. , Corfe Bernard M.
Published: January 2008

Butyrate is a critical cancer‐preventive element in the colon milieu whose mechanism of action is unclear, but appears to be mediated through inhibition of histone deacetylases (HDACs) and consequent alterations in global protein acetylation. Cytokeratins (CKs) have roles in cytoskeletal function as components of the intermediate filaments (IFs) and this involves CKs in the regulation of tissue homeostasis of high‐turnover epithelia such as the colon. We used a 2‐D gel/MS analysis to characterise the proteome of IFs, and a novel monitoring‐initiated detection and sequencing (MIDAS) approach to identify acetylation sites on principal proteins. We report that CKs are highly acetylated in a colon cancer cell line, with five acetylation sites characterised on CK8 and a further one on CK18. Acetylation of CK8 is responsive to butyrate. HDAC5 is the deacetylase associated with IFs. These data indicate a novel action of butyrate as a cancer preventive agent. Acetylation of CK8 may be associated with IFs stabilisation and thereby provide a candidate mechanism for the appropriate retention or loss of epithelial cells from the flat mucosa.
Detection and identification of plasma proteins that bind GlialCAM using ProteinChip™ Arrays, SELDI‐TOF MS, and nano‐LC MS/MS
Authors: Favre‐Kontula Linda , Sattonnet‐Roche Pascale , Magnenat Edith , Proudfoot Amanda E. I. , Boschert Ursula , Xenarios Ioannis , Vilbois Francis , Antonsson Bruno
Published: January 2008

In order to fully understand biological processes it is essential to identify interactions in protein complexes. There are several techniques available to study this type of interactions, such as yeast two‐hybrid screens, affinity chromatography, and coimmunoprecipitation. We propose a novel strategy to identify protein–protein interactions, comprised of first detecting the interactions using ProteinChips and SELDI‐TOF MS, followed by the isolation of the interacting proteins through affinity beads and RP‐HPLC and finally identifying the proteins using nano‐LC MS/MS. The advantages of this new strategy are that the primary high‐throughput screening of samples can be performed with small amounts of sample, no specific antibody is needed and the proteins represented on the SELDI‐TOF MS spectra can be identified with high confidence. Furthermore, the method is faster and less labor‐intensive than other current approaches. Using this novel method, we isolated and identified the interactions of two mouse plasma proteins, mannose binding lectin C and properdin, with GlialCAM, a type 1 transmembrane glycoprotein that belongs to the Ig superfamily.
Tools for analyzing and predicting N‐terminal protein modifications
Authors: Meinnel Thierry , Giglione Carmela
Published: January 2008

The vast majority of the proteins encoded in any genome naturally undergo a large number of different N‐terminal modifications, hindering their characterization by routine proteomic approaches. These modifications are often irreversible, usually cotranslational and are crucial, as their occurrence may reflect or affect the status, fate and function of the protein. For example, large signal peptide cleavages and N‐blocking mechanisms reflect targeting to various cell compartments, whereas N‐ligation events tend to be related to protein half‐life. N‐terminal positional proteomic strategies hold promise as a new generation of approaches to the fine analysis of such modifications. However, further biological investigation is required to resolve problems associated with particular low‐abundance or challenging N‐terminal modifications. Recent progress in genomics and bioinformatics has provided us with a means of assessing the impact of these modifications in proteomes. This review focuses on methods for characterizing the occurrence and diversity of N‐terminal modifications and for assessing their contribution to function in complete proteomes. Progress is being made towards the annotation of databases containing information for complete proteomes, and should facilitate research into all areas of proteomics.
Phosphoproteomic analysis of Leishmania donovani pro‐ and amastigote stages
Authors: Morales Miguel A. , Watanabe Reiko , Laurent Christine , Lenormand Pascal , Rousselle Jean‐Claude , Namane Abdelkader , Späth Gerald F.
Published: January 2008

Following transmission to the vertebrate host, the protozoan parasite Leishmania donovani differentiates into the pathogenic amastigote stage that is adapted for intracellular survival. This developmental transition is induced by environmental factors including elevated temperature and acidic pH and is likely transduced by signaling cascades involving protein kinases and their downstream phosphoprotein substrates. These signaling networks are highly adapted to the specific nutritional and physiological requirements of the organism and thus studying Leishmania phosphorylation may allow important insight into the parasite‐specific biology. We used a gel‐based approach to investigate qualitative and quantitative changes of the phosphoproteome of the major L. donovani life cycle stages. Phosphoproteins were purified by immobilized metal affinity chromatography (IMAC), separated by IEF and SDS‐PAGE using pH 4–7 IPG immobiline strips, revealed by fluorescent multiplex staining, and identified by MALDI‐MS and MS/MS. Our analysis allowed us to establish a first repertoire of the Leishmania phosphoproteome and to identify phosphoproteins implicated in stress‐ and heat shock response, RNA/protein turnover, metabolism, and signaling.
MPA: A multiple peak alignment algorithm to perform multiple comparisons of liquid‐phase proteomic profiles
Authors: Toppo Stefano , Roveri Antonella , Vitale Maria Pia , Zaccarin Mattia , Serain Elena , Apostolidis Emanuele , Gion Massimo , Maiorino Matilde , Ursini Fulvio
Published: January 2008

Present proteomic studies increasingly address experimental strategies focused on multiple comparisons of proteomic profiles. To accomplish semiautomatic protein separations based on 2‐D LC, the Beckman Coulter PF2D has been developed. Here, we present a novel general purpose tool called MPA (multiple peak alignment) able to perform multiple comparisons of proteomic profiles both in a pairwise guided fashion and in a fully automatic mode using a strategy based on dynamic programing and progressive alignment of time series. The tool is available at http://grup.cribi.unipd.it/people/stefano/mpa/.
Identification of collapsin response mediator protein‐2 as a potential marker of colorectal carcinoma by comparative analysis of cancer cell secretomes
Authors: Wu Chih‐Ching , Chen Hua‐Chien , Chen Su‐Jen , Liu Hao‐Ping , Hsieh Yi‐Yueh , Yu Chia‐Jung , Tang Reiping , Hsieh Ling‐Ling , Yu Jau‐Song , Chang Yu‐Sun
Published: January 2008

The cancer cell secretome may contain many potentially useful biomarkers. We therefore sought to identify proteins in the conditioned media of colorectal carcinoma (CRC) cell lines but not in those from other cancer cell lines. The secretomes of 21 cancer cell lines derived from 12 cancer types were analyzed by SDS‐PAGE combined with MALDI‐TOF MS. Among the 325 proteins identified, collapsin response mediator protein‐2 (CRMP‐2) was chosen for evaluation as a potential CRC biomarker, since it was selectively detected in the CRC cell line secretome and has never been reported as a cancer biomarker. Immunohistochemical analysis of 169 CRC specimens showed that CRMP‐2 was positively detected in 58.6% of the tumors, but weakly or not detected in >90% of the adjacent nontumor epithelial cells. Moreover, the CRMP‐2‐positive rate was significantly increased in earlier stage tumors and lymph node metastasis. Plasma CRMP‐2 levels were significantly higher in CRC patients (N = 201) versus healthy controls (N = 201) (61.3 ± 34.6 vs. 40.2 ± 24.3 ng/mL, p = 0.001). Our results indicate that comparative analysis of cancer cell secretome is a feasible strategy for identifying potential cancer biomarkers, and that CRMP‐2 may be a novel CRC biomarker.
Glutathione‐S‐transferase pi as a model protein for the characterisation of chemically reactive metabolites
Authors: Jenkins Rosalind E. , Kitteringham Neil R. , Goldring Christopher E. P. , Dowdall Samantha M. J. , Hamlett Jane , Lane Catherine S. , Boerma Jan‐Simon , Vermeulen Nico P. E. , Park B. Kevin
Published: January 2008

Chemically reactive metabolites (CRMs) are thought to be responsible for a number of adverse drug reactions through modification of critical proteins. Methods that defined the chemistry of protein modification at an early stage would provide invaluable tools for drug safety assessment. Here, human GST pi (GSTP) was exploited as a model target protein to determine the chemical, biochemical and functional consequences of exposure to the hepatotoxic CRM of paracetamol (APAP), N‐acetyl‐p‐benzoquinoneimine (NAPQI). Site‐specific, dose‐dependent modification of Cys47 in native and His‐tagged GSTP was revealed by MS, and correlated with inhibition of glutathione (GSH) conjugating activity. In addition, the adaptation of iTRAQ labelling technology to define precisely the quantitative relationship between covalent modification and protein function is described. Multiple reaction monitoring (MRM)‐MS of GSTP allowed high sensitivity detection of modified peptides at physiological levels of exposure. Finally, a bioengineered mutant cytochrome P450 with a broad spectrum of substrate specificities was used in an in vitro reaction system to bioactivate APAP: in this model, GSTP trapped the CRM and exhibited both reduced enzyme activity and site‐specific modification of the protein. These studies provide the foundation for the development of novel test systems to predict the toxicological potential of CRMs produced by new therapeutic agents.
The 1st European Summer School on ‘Proteomic Basics’ – The Students View 12–18 August, 2007 Kloster Neustift, Brixen/Bressanone, South Tyrol, Italy
Authors: Collins Emily S. , Little Samantha J.
Published: January 2008

Fifty postgraduate and postdoctoral delegates from all over Europe attended the week‐long ‘1st European Summer School on Proteomic Basics’ in Kloster Neustift in the Italian South Tyrol in August 2007. Invited proteomics experts gave tutorial lectures on Proteomics techniques with an emphasis on sample preparation, protein separation and purification in the first of an annual series of Proteomics Summer Schools funded by the EU and the Volkswagen Stiftung.
Growth hormone action in the developing neural retina: A proteomic analysis
Authors: Baudet Marie‐Laure , Hassanali Zahra , Sawicki Grzegorz , List Edward O. , Kopchick John J. , Harvey Steve
Published: January 2008

The possible presence and action of growth hormone (GH) in the neural retina was investigated in newborn mice. The neural retina was found to be a site of GH gene expression, as GH mRNA was abundant in cells of the retinal ganglion cell layer, in which GH was also detected. It was also a site of GH action, since GH receptor (GHR) immunoreactivity mirrored that of GH. Actions of GH within the eye were indicated by a reduction in its axial length and retinal width (its neuroblastic, inner plexiform, and optic fiber layers) in GHR gene disrupted mice (GHR−/−), in comparison with wild type (GHR+/+) littermates. In the absence of GH signaling, four proteins in the retinal proteome of the GHR−/− mice (identified by 2‐D gels and MS) differed in abundance with those in the wild type mice. Brain abundant membrane attached signal protein‐1 (BASP‐1) was down‐regulated, whereas protein kinase C inhibitor 1, cyclophilin A, KH domain‐containing, RNA‐binding, signal transduction‐associated protein 3 were up‐regulated in GHR−/− mice. These proteins are involved in retinal vascularization, neural proliferation and neurite outgrowth. GH might thus have hitherto unsuspected roles in these processes during retinal development.
Nucleophilicity of metal carbonyl anions in vinylic substitution reactions
Authors: Sazonov Petr K. , Artamkina Galina A. , Beletskaya Irina P.
Published: January 2008

Second order rate constants are reported for the reactions of metal carbonyl anions ([M(CO)nL]−) with several vinyl halides: PhCClC(CN)2, Z‐ and E‐Ph(CN)CCHHal (Hal = Cl, Br) which follow the addition–elimination (AdNE) substitution mechanism. The obtained data show that the nucleophilic reactivity of [M(CO)nL]− anions towards vinyl halides increases in the same order as in aliphatic SN2 reactions, but much more steeply, by 14 orders of magnitude in the row log{$k_{[{\bf M}({\bf CO})_n {\bf L}]{\bf M'}} {\rm /}k_{[{\bf CpMo}({\bf CO})_3 ]{\bf K}}$}: [CpFe(CO)2]− (∼14), [Re(CO)5]− (7.8), [Mn(CO)5]− 2.1, [CpW(CO)3]− (0.7) > [CpMo(CO)3]− (0). A good correlation exists between nucleophilicities of [M(CO)nL]− anions towards vinyl (sp2‐carbon) and alkyl halides (sp3‐carbon) with slope 2.7. The reactivity of [M(CO)nL]− in a halogen–metal exchange process (with Z‐PhC(CN)CHI) follows a similar ‘large’ scale as in the AdNE process. The nucleophilicity of [M(CO)nL]− anions correlates better with their one‐electron oxidation potentials (Eox) than with their basicity (pKa of [M(CO)nL]H). Copyright © 2008 John Wiley & Sons, Ltd.
Ethnicity and participation in cancer self‐help groups
Authors: Avis Mark , Elkan Ruth , Patel Seeta , Walker Barbara‐Anne , Ankti Neruma , Bell Caroline
Published: January 2008

Objectives: Investigations of the benefits of membership of a cancer self‐help group have suggested that it leads to improved sense of support, increased ability to deal with life‐events, and decreased anxiety, confusion, depression and helplessness. However, some evidence suggests that people from black and ethnic groups are less likely to join a cancer self‐help group. The main aims of the reported study were: to explore possible reasons why people from some ethnic groups have not participated in self‐help to the same extent as the rest of the community; and to identify ways in which participation of people from ethnic groups can be increased.

Methods: A qualitative interview‐based study of 68 people active in self‐help was carried out as a partnership between an academic institution and a community organisation.

Results: A thematic analysis of the interview transcripts identified three main aspects of the value of being a member of a self‐help group, regardless of interviewees' self‐identified ethnicity: forming a sense of togetherness, learning from one other, and developing mutuality. We identify a number of reasons that discourage or encourage people from black and ethnic groups to join cancer self‐help groups.

Conclusion: We discuss some limits, identified by interviewees, that affect development of feelings of togetherness and mutuality and we conclude with some brief recommendations about widening participation in cancer self‐help. Copyright © 2008 John Wiley & Sons, Ltd.
Beliefs about cancer causation and prevention as a function of personal and family history of cancer: a national, population‐based study
Authors: Lykins Emily L. B. , Graue Lili O. , Brechting Emily H. , Roach Abbey R. , Gochett Celestine G. , Andrykowski Michael A.
Published: January 2008

Objective: Research suggests individuals possess multifaceted cognitive representations of various diseases. These illness representations consist of various beliefs, including causal attributions for the disease, and are believed to motivate, guide, and shape health‐related behavior. As little research has examined factors associated with beliefs about cancer causation, this study examined the relationship between personal and family history of cancer and beliefs about the causes and prevention of malignant disease.

Methods: Data were obtained from 6369 adult respondents to the 2003 Health Information National Trends Survey, a national population‐based survey. Information about personal and family history of cancer and beliefs regarding cancer causation and prevention was obtained.

Results: Results showed both a personal and family history of cancer were associated with differences in beliefs about the causes of cancer. In general, a personal history of cancer was not significantly linked to causal attributions for cancer relative to those without a personal history. In contrast, a family history of cancer tended to increase the likelihood a respondent viewed a particular cause as increasing cancer risk. Thus, personal and vicarious experience with cancer had dramatically diverging influences on attributions of cancer causation, which may be due to differing self‐protection motives.

Conclusion: Results support the belief that illness representations, in this case the causal belief component, are influenced by both personal and vicarious experience with a disease and also suggest illness representations may influence receptivity to messages and interventions designed to increase appropriate cancer risk reduction behavior. Copyright © 2007 John Wiley & Sons, Ltd.
The EORTC QLQ‐CX24 cervical cancer‐specific quality of life questionnaire: psychometric properties in a South Asian sample of cervical cancer patients
Authors: Jayasekara Harindra , Rajapaksa Lalini C. , Greimel Elfriede R.
Published: January 2008

Objective: The cervical cancer‐specific Quality of Life module of the European Organization for Research and Treatment of Cancer, EORTC QLQ‐CX24, was recently validated in an international field study that did not include cervical cancer patients from South Asia. The aim of our study was to assess the psychometric properties of the instrument in a sample of cervical cancer patients from Sri Lanka to assess its suitability for use in the South Asian region.

Methods: One hundred and twelve newly diagnosed patients with cervical cancer completed the translated version of the QLQ‐CX24 in a cross‐sectional validation study. Psychometric evaluation assessed the instrument for scale structure, scale reliability, validity and acceptability.

Results: The QLQ‐CX24 was found to be patient‐friendly with high compliance and low missing data. Only a few patients needed assistance for completion. Overall results for multitrait scaling analysis confirmed the scale structure although some items of the symptom experience scale exhibited problems regarding item‐scale correlations with its own scale. Cronbach's alpha coefficients for internal consistency ranging from 0.63 to 0.79 confirmed scale reliability. Construct validity was confirmed in two ways: the inter‐scale correlations were statistically significant (p<0.01) and their magnitude moderate (r = 0.52–0.58) while the scales and single‐item measures were able to discriminate between subgroups of patients differing with regard to treatment status.

Conclusion: The translated version of the QLQ‐CX24 is a reliable and valid instrument to measure cervical cancer‐specific Quality of Life in Sri Lanka. The overall results are in line with the findings of the international field study. Copyright © 2007 John Wiley & Sons, Ltd.
Socio‐demographic, psychosocial and attitudinal predictors of help seeking after cancer diagnosis
Authors: Steginga Suzanne K. , Campbell Alistair , Ferguson Megan , Beeden Alison , Walls Melissa , Cairns Will , Dunn Jeff
Published: January 2008

Objective: The objective is to describe cancer patients' patterns of use of psychosocial support services and identify socio‐demographic, psychosocial, and attitudinal predictors of service utilization.

Methods: A cross‐sectional survey of 439 cancer patients (61.2% response) at a regional tertiary cancer center assessed patterns of support service utilization, cancer‐specific distress, social support and constraints, and attitudes to help seeking.

Results: Patients less frequently received advice about psychosocial support in comparison with treatment‐related information. More than half the respondents were aware of social work support, support groups, and chaplain support; however, most did not utilize these services. For unaware patients, up to 47% would have utilized support services if they had known of their existence. The use of services was significantly related to being female, younger, and having greater cancer‐specific distress, more positive and less negative attitudes to help seeking. Future intention to contact a health professional for psychological support was predicted by more positive subjective norms and outcome expectations, higher cancer‐specific distress, and less negative attitudes to help seeking.

Conclusion: Initiatives that encourage distressed patients to use psychosocial care services should highlight positive outcomes. Educational programs for health professionals to support psychosocial care in oncology are needed. Copyright © 2008 John Wiley & Sons, Ltd.