bluuebunny/crossref_metadata_2025 huggingface dataset:
Toxicity of radiotherapy in patients with collagen vascular disease
Authors: Lin Alexander , Abu‐Isa Eyad , Griffith Kent A. , Ben‐Josef Edgar
Published: May 2008

BACKGROUND.

A diagnosis of collagen vascular disease (CVD) may predispose to radiotherapy (RT) toxicity. The objective of the current study was to identify factors that influence RT toxicity in the setting of CVD.

METHODS.

A total of 86 RT courses for 73 patients with CVD were delivered between 1985 and 2005. CVD subtypes include rheumatoid arthritis (RA; 33 patients), systemic lupus erythematosus (SLE; 13 patients), scleroderma (9 patients), dermatomyositis/polymyositis (5 patients), ankylosing spondylitis (4 patients), polymyalgia rheumatica/temporal arteritis (4 patients), Wegener granulomatosis (3 patients), and mixed connective tissue disorders (MCTD)/other (2 patients). Each patient with CVD was matched to 1 to 3 controls with respect to sex, race, site irradiated, RT dose (±2 Gray), and age (±5 years).

RESULTS.

There was no significant difference between CVD patients (65.1%) and controls (72.5%) experiencing any acute toxicity. CVD patients had a higher incidence of any late toxicity (29.1% vs 14%; P = .001), and a trend toward an increased rate of severe late toxicity (9.3% vs 3.7%; P = .079). RT delivered to the breast had increased risk of severe acute toxicity, whereas RT to the pelvis had increased risk of severe acute and late toxicity. RT administered in the setting of scleroderma carried a higher risk of severe late toxicity, whereas RT to SLE patients carried a higher risk of severe acute and late toxicity.

CONCLUSIONS.

Although generally well tolerated, RT in the setting of CVD appears to carry a higher risk of late toxicity. RT to the pelvis or in the setting of SLE or scleroderma may predispose to an even greater risk of severe toxicity. These issues should be considered when deciding whether to offer RT for these patients. Cancer 2008. © 2008 American Cancer Society.
Interaction of CJX2, an amlodipine derivative with human P‐glycoprotein ATPase activity
Authors: Ji Bian‐Sheng , He Ling
Published: May 2008

P‐glycoprotein, a plasma membrane protein overexpressed in multidrug‐resistant (MDR) cells, is responsible for the energy‐dependent efflux of structurally unrelated cytotoxic agents and MDR‐reversing drugs from the cells. Understanding the interaction of P‐gp reversing agents with P‐gp ATPase activity should provide useful information for understanding the mechanisms of P‐gp modulator. The aim of present report was to elucidate the possible mechanism of CJX2, an amlodipine derivative, in modulating P‐gp function by determining its effect on P‐gp ATPase activity. Basal P‐gp ATPase activity in K562/DOX cells was increased by CJX2 with a half‐maximal activity concentration (Km) of 10.7±1.8 µM. Kinetic analysis indicated a noncompetitive inhibition of verapamil (Ver)‐stimulated P‐gp ATPase activity by CJX2 and a competitive inhibition of CJX2‐stimulated P‐gp ATPase activity by tetrandrine; moreover, the effect of Cyclosporin A (CsA) on CJX2‐stimulated and Ver‐stimulated P‐gp ATPase activity showed noncompetitive and a competitive inhibition, respectively. CJX2 and Tet can bind P‐gp either on overlapping sites or distinct but interacting sites, while CJX2 and Ver as well as CsA can bind P‐gp on separate sites in K562/DOX cells. Drug Dev Res 69:42–47, 2008 © 2008 Wiley‐Liss, Inc.
HLA‐DM negatively regulates HLA‐DR4‐restricted collagen pathogenic peptide presentation and T cell recognition
Authors: Amria Shereen , Hajiaghamohseni Laela M. , Harbeson Caroline , Zhao Dan , Goldstein Oliver , Blum Janice S. , Haque Azizul
Published: May 2008

Rheumatoid arthritis, an autoimmune disease, is significantly associated with the HLA class II allele HLA‐DR4. While the etiology of rheumatoid arthritis remains unknown, type II collagen (CII) is a candidate autoantigen. An immunodominant pathogenic epitope from this autoantigen, CII261–273, which binds to HLA‐DR4 and activates CD4+ T cells, has been identified. The non‐classical class II antigen, HLA‐DM, is also a key component of class II antigen presentation pathways influencing peptide presentation by HLA‐DR molecules expressed on professional antigen‐presenting cells (APC). Here, we investigated whether the HLA‐DR4‐restricted presentation of the pathogenic CII261–273 epitope was regulated by HLA‐DM expression in APC. We show that APC lacking HLA‐DM efficiently display the CII261–273 peptide/epitope to activate CD4+ T cells, and that presentation of this peptide is modulated dependent on the level of HLA‐DM expression in APC. Mechanistic studies demonstrated that the CII261–273 peptide is internalized by APC and edited by HLA‐DM molecules in the recycling pathway, inhibiting peptide presentation and T cell recognition. These findings suggest that HLA‐DM expression in APC controls class II‐mediated CII261–273 peptide/epitope presentation and regulates CD4+ T cell responses to this self epitope, thus potentially influencing CII‐dependent autoimmunity.
Mutual antagonistic relationship between prostaglandin E2 and IFN‐γ: Implications for rheumatoid arthritis
Authors: Mathieu Marie‐Claude , Lord‐Dufour Simon , Bernier Virginie , Boie Yves , Burch Jason D. , Clark Patsy , Denis Danielle , Han Yongxin , Mortimer James R. , Therien Alex G.
Published: May 2008

Prostaglandin E2 (PGE2) is a major mediator of inflammation and is present at high concentrations in the synovial fluid of rheumatoid arthritis (RA) patients. PGE2, acting through the EP4 receptor, has both pro‐ and anti‐inflammatory roles in vivo. To shed light on this dual role of PGE2, we investigated its effects in whole blood and in primary human fibroblast‐like synoviocytes (FLS). Gene expression analysis in human leukocytes, confirmed at the protein level, revealed an EP4‐dependent inhibition of the expression of genes involved in the IFN‐γ‐activation pathway, including IFN‐γ itself. This effect of the PGE2/EP4 axis on IFN‐γ is a reciprocal phenomenon since IFN‐γ blocks PGE2 release and blocks EP receptor expression. The mutually antagonistic relationship between IFN‐γ and PGE2 extends to downstream cytokine and chemokine release; PGE2 counters the effects of IFN‐γ, on the release of IP‐10, IL‐8, TNF‐α and IL‐1β. To gain further insight into IFN‐γ‐mediated cellular events in RA, we assessed the effects of IFN‐γ on gene expression in FLS. We observed an IFN‐γ‐dependent up‐regulation of macrophage‐attracting chemokines, and down‐regulation of metalloprotease expression. These results suggest the existence of a mutually antagonistic relationship between PGE2 and IFN‐γ, which may represent a fundamental mechanism of immune control in diseases such as RA.

Supporting Information for this article is available at www.wiley‐vch.de/contents/jc_2040/2008/38170_s.pdf
Synthesis and Photophysical Properties of Silica‐Gel‐Supported Photofunctional (Phthalocyaninato)silicon Complexes
Authors: Ishii Kazuyuki , Kikukawa Yuu , Shiine Masahiko , Kobayashi Nagao , Tsuru Tatsuro , Sakai Yasuyuki , Sakoda Akiyoshi
Published: May 2008

The photophysical properties and surface structures of silica‐gel‐supported photofunctional (phthalocyaninato)silicon complexes (SiPc‐SiO2) were investigated in terms of their electronic absorption, fluorescence, singlet‐oxygen luminescence, and nitrogen adsorption/desorption isotherms. Thenitrogen/desorption isotherms indicate that the planes of SiPcs Aanchored by axial ligands are parallel to the silica gel surface. In the proposed structure the tetradentate Pc ligands are considered to coordinate with the silica gel particles, since central elements of SiPcs, such as Si–O–Si–OH, are similar to constituents of silica gel. It was shown that the addition of an organic solvent (chloroform, cyclohexane, etc.), whose refractive index is comparable to that of the silica gels, increases the transparency of the silica gels. This method of adding the solvent allows to quantitatively analyze the photophysical properties and is useful for investigating other modified silicas. The intensities of fluorescence and singlet‐oxygen luminescence decrease with an increase in the amount of SiPcs due to interactions between the SiPcs in aggregates. By changing the amount of SiPcs, solid materials were prepared based on Pc complexes with both monomeric photophysical properties and a high ability for singlet‐oxygen generation. The electronic absorption spectra of SiPc‐SiO2 indicate that a wide optical window is maintained between the Soret and Q absorption bands, even for high concentrations of SiPcs ([SiPc] ≈ 10–2 M). This results in deep‐green solids, which is unlike the blue color of the crystals or concentrated solutions (>10–5 M) of SiPc(OH)2. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)
Spectroscopic and Computational Study on New Blue Emitting ReL(CO)3Cl Complexes Containing Pyridylimidazo[1,5‐a]pyridine Ligands
Authors: Garino Claudio , Ruiu Tiziana , Salassa Luca , Albertino Andrea , Volpi Giorgio , Nervi Carlo , Gobetto Roberto , Hardcastle Kenneth I.
Published: May 2008

The structural and photophysical properties of three new ReL(CO)3Cl complexes (ReL1–ReL3) and their 1‐(2‐pyridyl)imidazo[1,5‐a]pyridine ligands, namely 3‐methyl‐1‐(2‐pyridyl)imidazo[1,5‐a]pyridine (L1), 1‐(2‐pyridyl)‐3‐[4‐(trifluoromethyl)phenyl]imidazo[1,5‐a]pyridine (L2), and 3‐(4‐nitrophenyl)‐1‐(2‐pyridyl)imidazo[1,5‐a]pyridine (L3), were studied by spectroscopy, X‐ray diffraction, and computational methods. ReL1–ReL3 have high‐energy singlet emissions arising from a π → π* ligand‐centered state. In oxygen‐free acetonitrile solutions, the complexes display dual fluorescence due to intense ligand‐centered triplet emission.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)
A New Multicomponent Reaction Catalyzed by a Lewis Acid Catalyst: Convenient Synthesis of Polyfunctional Tetrahydropyr­imidines
Authors: Zhang Min , Jiang Huan‐Feng
Published: May 2008

A novel and convenient one‐pot synthesis of polyfunctional tetrahydropyrimidine analogues through a Lewis acid catalyzed multicomponent reaction is disclosed. This domino reaction proceeds smoothly in moderate‐to‐good yields with formation of four C–N bonds in one step. The products are interesting nitrogen heterocycles that contain α‐ and β‐amino acid blocks. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)
Chemistry with [18F]Fluoride Ion (Eur. J. Org. Chem. 17/2008)
Authors: Cai Lisheng , Lu Shuiyu , Pike Victor W.
Published: May 2008

The cover picture shows the “Chemistry with [18F]Fluoride Ion?”in PET radiotracer production. The procedure includes: (i) production of aqueous [18F]fluoride ion from the cyclotron‐promoted 18O(p,n)18F nuclear reaction on 18O‐enriched water, (ii) conversion of the aqueous [18F]fluoride ion into a more nucleophilic species by complexation with kryptand‐K+, (iii) incorporation of fluorine‐18 into a radiotracer, namely [18F]SP203, for brain mGluR5 receptors, (iv) positron emission tomography (PET) of the radiotracer in a human subject, and (v) generation of the corresponding PET image of the brain mGluR5 receptor distribution. These steps are presented over a clock background to stress the necessity to work quickly and efficiently with short‐lived fluorine‐18 (t1/2 = 109.7 min) and according to a tight time schedule from radionuclide production through to PET imaging. Details are presented in the Microreview by L. S. Cai, S. Y. Lu and V. W. Pike on p. 2853 ff. The authors thank Dr. A. K. Brown and other staff of the Molecular Imaging Branch at the National Institute of Mental Health (Bethesda, Maryland, USA) for the generation of the PET image.
Strategic evaluation of research and development in Japan's public research institutes
Authors: Nakamura Osamu , Nakamura Osamu , Sawada Michiko Takagi , Kosaka Shin , Koyanagi Masao , Matsunaga Isao , Mizuno Koichi , Kobayashi Naoto
Published: May 2008

The authors describe a strategic evaluation system for research and development (R&D) in Japan's public research institutes, using examples implemented in the National Institute of Advanced Industrial Science and Technology (AIST). Important issues include promoting coherent and concurrent research on the basis of a strategy to bring about outcomes, and performing the evaluation from the perspective of outcomes in order to develop a clear scenario that might be related to future innovations. © Wiley Periodicals, Inc.
Forecasting euro area variables with German pre‐EMU data
Authors: Brüggemann Ralf , Lütkepohl Helmut , Marcellino Massimiliano
Published: May 2008

It is investigated whether euro area variables can be forecast better based on synthetic time series for the pre‐euro period or by using just data from Germany for the pre‐euro period. Our forecast comparison is based on quarterly data for the period 1970Q1–2003Q4 for 10 macroeconomic variables. The years 2000–2003 are used as forecasting period. A range of different univariate forecasting methods is applied. Some of them are based on linear autoregressive models and we also use some nonlinear or time‐varying coefficient models. It turns out that most variables which have a similar level for Germany and the euro area such as prices can be better predicted based on German data, while aggregated European data are preferable for forecasting variables which need considerable adjustments in their levels when joining German and European Monetary Union (EMU) data. These results suggest that for variables which have a similar level for Germany and the euro area it may be reasonable to consider the German pre‐EMU data for studying economic problems in the euro area. Copyright © 2008 John Wiley & Sons, Ltd.
Insulin induces calcium signals in the nucleus of rat hepatocytes
Authors: Rodrigues Michele A. , Gomes Dawidson A. , Andrade Viviane A. , Leite Fatima M. , Nathanson Michael H.
Published: May 2008

Insulin is an hepatic mitogen that promotes liver regeneration. Actions of insulin are mediated by the insulin receptor, which is a receptor tyrosine kinase. It is currently thought that signaling via the insulin receptor occurs at the plasma membrane, where it binds to insulin. Here we report that insulin induces calcium oscillations in isolated rat hepatocytes, and that these calcium signals depend upon activation of phospholipase C and the inositol 1,4,5-trisphosphate receptor, but not upon extracellular calcium. Furthermore, insulin-induced calcium signals occur in the nucleus, and are temporally associated with selective depletion of nuclear phosphatidylinositol bisphosphate and translocation of the insulin receptor to the nucleus. These findings suggest that the insulin receptor translocates to the nucleus to initiate nuclear, inositol 1,4,5-trisphosphate-mediated calcium signals in rat hepatocytes. This novel signaling mechanism may be responsible for insulin's effects on liver growth and regeneration. (Hepatology 2008.)
Evaluation of risk factors in the development of hepatocellular carcinoma in autoimmune hepatitis: Implications for follow-up and screening
Authors: Yeoman Andrew D. , Al-Chalabi Thawab , Karani John B. , Quaglia Alberto , Devlin John , Mieli-Vergani Giorgina , Bomford Adrian , O'Grady John G. , Harrison Phillip M. , Heneghan Michael A.
Published: May 2008

Hepatocellular carcinoma (HCC) has traditionally been considered a rare complication of cirrhosis secondary to autoimmune hepatitis (AIH), yet the true incidence remains unknown due to a lack of published data. Consequently, some professional guidelines do not mandate routine surveillance for HCC in this condition. Our aims were to evaluate the rate at which HCC develops among a large, prospectively obtained cohort of patients with AIH at a single center. Demographic, clinical, and laboratory indices associated with the development of HCC were also identified. HCC was discovered in 15 of 243 patients with AIH, all of whom had type 1 AIH equating to 1090 cases per 100,000 patient follow-up years. HCC occurred in the same proportion of females as males, 6.1% versus 6.4%,

P

= 0.95. HCC occurred more frequently in patients who had cirrhosis at presentation, 9.3% versus 3.4%,

P

= 0.048, or who had a variceal bleed as the index presentation of AIH, 20% versus 5.3%,

P

= 0.003. The median duration from time of confirmed cirrhosis to a diagnosis of HCC was 102.5 months, range 12-195 months. Median survival in patients whose HCC was diagnosed on surveillance was 19 months (range 6-36 months) compared with 2 months (range 0-14 months) for patients presenting symptomatically (

P

= 0.042).

Conclusion:

Cirrhosis in AIH is the

sine qua non

for HCC development, which subsequently occurs at a rate of 1.1% per year and affects men and women in equal proportions. (Hepatology 2008.)
Acute toxoplasmosis in nonstem cell transplant patients with haematological malignancies: a study from a regional cancer institute in South India
Authors: Adurthi S , Sahoo TP , Chakka Kumar , Radhika B , Appaji L , Bapsy PP , Ramesh C , Jayshree RS
Published: May 2008

The frequency of Toxoplasma gondii (Tgondii) infections was investigated during febrile episodes in nonstem cell transplant patients with haematological malignancies (HM). One hundred and sixty‐two febrile episodes in 125 HIV‐negative patients with HM undergoing treatment at Kidwai Memorial Institute of Oncology, Bangalore, India comprised the study group. Plasma from anticoagulated whole blood was used for amplifying the B1 gene of T. gondii by nPCR. Specific antibodies to T. gondii (IgM and IgG) were tested using commercial kits. Corticosteroid and cotrimoxazole usage during these episodes was 50 and 41%, respectively. Twenty‐two of the febrile episodes (14%) were positive for T. gondii; nine of which did not have any other concomitant infecting pathogen and were seen in symptomatic patients. While majority of these (13%) were ‘Toxoplasma infection’, there was a single case of ‘probable Toxoplasma disease’ (0.6%). In four of the fatal febrile episodes, T. gondii was the causative agent; two of which did not have any other concomitant infection. None of the patients had undergone stem cell transplantation. Copyright © 2008 John Wiley & Sons, Ltd.
Hydrological behaviour and modelling of a volcanic tropical cultivated catchment
Authors: Charlier Jean‐Baptiste , Cattan Philippe , Moussa Roger , Voltz Marc
Published: May 2008

The hydrological behaviour of the cultivated Féfé catchment (17·8 ha) on the tropical volcanic island of Guadeloupe was studied to identify flow paths, to quantify water fluxes, and finally, to build a lumped model to simulate discharge and piezometer levels. The approach combined two steps, an experimental step and a modelling step, which covered two time scales, the annual and the storm event scale. The hydrological measurements were conducted over 2 years. The Féfé catchment is characterized by heavy rainfall (4229 mm year−1) on permeable Andosols; the results showed that underground flow paths involved two overlapping aquifers, and that the annual water balance in 2003 was shared among outflows of the deep aquifer (42%), evapotranspiration (31%), and streamflow (27%). On the event scale, the surface runoff coefficient ranges between 6·2% and 24·4% depending on antecedent dry or wet moisture conditions. Hortonian overland flow predominated over subsurface and saturation overland flow processes. Recharge of the shallow aquifer is mainly governed by a constant infiltration capacity of the Andosols with depth in the vadose zone. Outflows of this shallow aquifer were the baseflow of the main stream and the recharge of the deep aquifer. Volcanic deposits at Féfé promoted the underground flow path, and cultivated areas seemed to explain the high stormflow values relative to other tropical small catchments under rain forest. A conceptual lumped model integrating runoff, infiltration, evapotranspiration, and fluctuations of the two overlapping aquifers was developed. The model has six parameters and was calibrated and validated on the hydrograph at the outlet and on the two piezometers of the shallow and the deep aquifers. The results show fair to good agreement between measured and simulated variables, and consequently, the model was consistent with the main hydrological processes observed from experimental results in wet conditions. Copyright © 2008 John Wiley & Sons, Ltd.
Frequency analysis for predicting 1% annual maximum water levels along Florida coast, US
Authors: Xu Sudong , Huang Wenrui
Published: May 2008

In the Coastal Flood Insurance Study by the Federal Emergency Management Agency (FEMA, 2005), 1% annual maximum coastal water levels are used in coastal flood hazard mitigation and engineering design in coastal areas of USA. In this study, a frequency analysis method has been developed to provide more accurate predictions of 1% annual maximum water levels for the Florida coast waters. Using 82 and 94 years of annual maximum water level data at Pensacola and Fernandina, performances of traditional frequency analysis methods, including advanced method of Generalized Extreme Value distribution method, have been evaluated. Comparison with observations of annual maximum water levels with 83 and 95 years of return periods indicate that traditional methods are unable to provide satisfactory predictions of 1% annual maximum water levels to account for hurricane‐induced extreme water levels. Based on the characteristics of annual maximum water level distribution of Pensacola and Fernandina stations, a new probability distribution method has been developed in this study. Comparison with observations indicates that the method presented in this study significantly improves the accuracy of predictions of 1% annual maximum water levels. For Fernandina station, predictions of extreme water level match well with the general trend of observations. With a correlation coefficient of 0·98, the error for the maximum observed extreme water level of 3·11 m (National Geodetic Vertical Datum) with 95 years of return period is 0·92%. For Pensacola station, the prediction error for the maximum observed extreme water level with a return period of 83 years is 5·5%, with a correlation value of 0·98. The frequency analysis has also been reasonably compared to the more costly Monte Carlo simulation method. Copyright © 2008 John Wiley & Sons, Ltd.
Modelling runoff from highly glacierized alpine drainage basins in a changing climate
Authors: Huss Matthias , Farinotti Daniel , Bauder Andreas , Funk Martin
Published: May 2008

The future runoff from three highly glacierized alpine catchments is assessed for the period 2007–2100 using a glacio‐hydrological model including the change in glacier coverage. We apply scenarios for the seasonal change in temperature and precipitation derived from regional climate models. Glacier surface mass balance and runoff are calculated in daily time‐steps using a distributed temperature‐index melt and accumulation model. Model components account for changes in glacier extent and surface elevation, evaporation and runoff routing. The model is calibrated and validated using decadal ice volume changes derived from four digital elevation models (DEMs) between 1962 and 2006, and monthly runoff measured at a gauging station (1979–2006). Annual runoff from the drainage basins shows an initial increase which is due to the release of water from glacial storage. After some decades, depending on catchment characteristics and the applied climate change scenario, runoff stabilizes and then drops below the current level. In all climate projections, the glacier area shrinks dramatically. There is an increase in runoff during spring and early summer, whereas the runoff in July and August decreases significantly. This study highlights the impact of glaciers and their future changes on runoff from high alpine drainage basins. Copyright © 2008 John Wiley & Sons, Ltd.
Analytical power series solutions to the two‐dimensional advection–dispersion equation with distance‐dependent dispersivities
Authors: Chen Jui‐Sheng , Ni Chuen‐Fa , Liang Ching‐Ping
Published: May 2008

As is frequently cited, dispersivity increases with solute travel distance in the subsurface. This behaviour has been attributed to the inherent spatial variation of the pore water velocity in geological porous media. Analytically solving the advection–dispersion equation with distance‐dependent dispersivity is extremely difficult because the governing equation coefficients are dependent upon the distance variable. This study presents an analytical technique to solve a two‐dimensional (2D) advection–dispersion equation with linear distance‐dependent longitudinal and transverse dispersivities for describing solute transport in a uniform flow field. The analytical approach is developed by applying the extended power series method coupled with the Laplace and finite Fourier cosine transforms. The developed solution is then compared to the corresponding numerical solution to assess its accuracy and robustness. The results demonstrate that the breakthrough curves at different spatial locations obtained from the power series solution show good agreement with those obtained from the numerical solution. However, owing to the limited numerical operation for large values of the power series functions, the developed analytical solution can only be numerically evaluated when the values of longitudinal dispersivity/distance ratio eL exceed 0·075. Moreover, breakthrough curves obtained from the distance‐dependent solution are compared with those from the constant dispersivity solution to investigate the relationship between the transport parameters. Our numerical experiments demonstrate that a previously derived relationship is invalid for large eL values. The analytical power series solution derived in this study is efficient and can be a useful tool for future studies in the field of 2D and distance‐dependent dispersive transport. Copyright © 2008 John Wiley & Sons, Ltd.
PKC alpha protein but not kinase activity is critical for glioma cell proliferation and survival
Authors: Cameron Angus J. , Procyk Katarzyna J. , Leitges Michael , Parker Peter J.
Published: May 2008

Protein kinase C alpha (PKCα) has been implicated in tumor development with high levels of PKCα expression being associated with various malignancies including glioblastomas and tumors of the breast and prostate. To account for its upregulation in these cancers, studies have suggested that PKCα plays a role in promoting cell survival. Here we show by siRNA depletion in U87MG glioma cells that a critical threshold level of PKCα protein expression is essential for their growth in the presence of serum and for their survival following serum deprivation. Derivation of PKCα wt and KO mouse embryo fibroblast cell lines confirms a role for PKCα in protecting cells from apoptosis induced by serum deprivation. Notably, PKCα was found to mediate chemo‐protection in these fibroblastic cell lines. In U87MG cells PKCα does not confer chemoprotection though this likely reflects growth arrest associated with its depletion. To determine the requirements for catalytic function, comparison was made between distinct classes of PKC inhibitors. In contrast to loss of PKCα protein, inhibition of PKC kinase activity in glioma cell lines does not significantly inhibit growth or survival. Conversely, inhibition with calphostin C, which targets the regulatory domain of PKC, potently inhibits proliferation and induces apoptosis. Evidence is presented that it is the fully phosphorylated, folded form of PKCα that confers this activity‐independent behaviour. These results indicate an essential pro‐proliferative and pro‐survival role for PKCα in glioma but question the use of ATP competitive inhibitors as therapeutics, either alone, or in combination with chemotoxic agents. © 2008 Wiley‐Liss, Inc.
Enhanced expression of NADPH oxidase Nox4 in human gliomas and its roles in cell proliferation and survival
Authors: Shono Tadahisa , Yokoyama Nobuhiko , Uesaka Toshio , Kuroda Junya , Takeya Ryu , Yamasaki Tomoko , Amano Toshiyuki , Mizoguchi Masahiro , Suzuki Satoshi O. , Niiro Hiroaki , Miyamoto Kyoko , Akashi Koichi , Iwaki Toru , Sumimoto Hideki , Sasaki Tomio
Published: May 2008

Reactive oxygen species (ROS) have been attracting attention as mediators of various cell‐signaling pathways. Nox‐family NADPH oxidases have proven to be a major source of ROS production in various cell types and have crucial roles in various physiological and pathological processes. In this study, we show that Nox4, a member of Nox family, is prominently expressed in various neuroepithelial tumors by reverse transcription‐polymerase chain reaction (RT‐PCR) and immunohistochemical studies. We quantified Nox4 mRNA expression by real‐time PCR in tumor specimens from 58 patients with astrocytomas and found that the expression levels of Nox4 mRNA in glioblastomas (WHO grade IV) were significantly higher than those in other astrocytomas (WHO grade II and III). In addition, we show that specific knockdown of Nox4 expression by RNA interference results in cell‐growth inhibition and enhances induction of apoptosis by chemotherapeutic agents, such as cisplatin, in cultured glioma cell lines. Based on these observations, enhanced expression of Nox4 appears to be involved in cell proliferation and survival in glioma cells. © 2008 Wiley‐Liss, Inc.
Risk of gastric cancer in asymptomatic, middle‐aged Japanese subjects based on serum pepsinogen and Helicobacter pylori antibody levels
Authors: Yanaoka Kimihiko , Oka Masashi , Yoshimura Noriko , Mukoubayashi Chizu , Enomoto Shotaro , Iguchi Mikitaka , Magari Hirohito , Utsunomiya Hirotoshi , Tamai Hideyuki , Arii Kenji , Yamamichi Nobutake , Fujishiro Mitsuhiro , Takeshita Tatsuya , Mohara Osamu , Ichinose Masao
Published: May 2008

A total of 5,209 asymptomatic, middle‐aged subjects, whose serum pepsinogen (PG) and Helicobacter pylori antibody levels had been assessed, were followed for 10 years. Subjects with positive serum H. pylori antibodies (>50 U/mL) had an increased cancer risk (HR = 3.48, 95% CI = 1.26–9.64). Risk of gastric cancer increased as the antibody level increased; the H. pylori‐positive group with antibody levels >500 U/mL had the highest incidence rate (325/100,000 person‐years). Cancer development also increased with a reduced serum PG I level or a reduced PG I/II ratio; the risk was significantly elevated with serum PG I level ≤30 ng/mL (HR = 3.54, 95% CI = 1.95–6.40) or PG I/II ratio ≤3.0 (HR = 4.25, 95% CI = 2.47–7.32). Furthermore, the risk of diffuse‐type cancer increased as PG II level increased; it was significantly elevated with PG II level ≥30 ng/mL (HR = 3.81, 95% CI = 1.10–13.21). Using H. pylori antibody and PG levels, subgroups with an especially high or low cancer incidence rate could be identified. H. pylori‐negative or indeterminate subjects with low PG level (PG I ≤30 ng/mL or PG I/II ratio ≤2.0) or H. pylori‐positive subjects with antibody levels >500 U/mL and a low PG level were among the subgroups with a high cancer incidence rate (over 400/100,000 person‐years). In contrast, H. pylori‐negative subjects with a PG I level >70 ng/mL or a PG I/II ratio >3.0 had the lowest risk; none of these subjects developed cancer. Thus, serum PG levels and/or H. pylori antibody levels can be used to predict the risk of cancer in individuals with H. pylori‐related gastritis from the general population. © 2008 Wiley‐Liss, Inc.
Single‐nucleotide polymorphism‐mass array reveals commonly deleted regions at 3p22 and 3p14.2 associate with poor clinical outcome in esophageal squamous cell carcinoma
Authors: Qin Yan Ru , Fu Li , Sham Pak C. , Kwong Dora L.W. , Zhu Cai Lei , Chu Kevin K.W. , Li Yan , Guan Xin‐Yuan
Published: May 2008

Esophageal squamous cell carcinoma (ESCC) is one of the most common solid tumors in the world with poor prognosis. Deletion of chromosome 3p is one of the most frequent chromosomal alterations in ESCC, suggesting the existence of one or more tumor suppressor genes (TSGs) at this region. In the present study, a recently developed high‐throughput and high‐resolution technology, single‐nucleotide polymorphism (SNP)‐mass array, was applied to investigate loss of heterozygosity on 3p in 100 primary ESCC cases with 386 SNP markers. Four commonly deleted regions (CDRs) at 3p26.3, 3p22, 3p21.3 and 3p14.2 were identified. Absent and down‐regulated expression of several candidate TSGs, including CHL1, PCAF, RBMS3, PLCD1 and CACNA2D3, were detected in primary ESCC tumors and ESCC cell lines. Moreover, deletions of CDRs 2 and 4 were correlated with advanced tumor stage and deletion of CDR2 was associated with tumor metastasis in ESCC. Our findings provided evidence that minimal deleted regions at 3p26.3, 3p22, 3p21.3 and 3p14.2 containing potential TSGs may contribute to the pathogenesis of esophageal cancer. © 2008 Wiley‐Liss, Inc.
Novel “anchor modification” of polymeric biomaterial surfaces by the utilization of cyclodextrin inclusion complex supramolecules
Authors: Zhao Xiaobin , Courtney James M.
Published: May 2008

In this article, a novel approach for the surface modification of polymeric biomaterials by the utilization of supramolecules was studied. The supramolecules selected were cyclodextrin inclusion complexes (CICs). The biomaterial selected for surface modification was plasticized poly (vinyl chloride) (PVC‐P). Results indicate that when the CICs were blended into PVC‐P, they tend to migrate and “anchor” on the surface to achieve a remarkable protein‐resistant surface, with improved blood compatibility. In comparison with a physical mixture of cyclodextrins and a “guest” molecule, such as poly(ethylene oxide) (PEO)‐poly(propylene oxide) (PPO)‐PEO and PPO‐PEO‐PPO for PVC‐P modification, CICs modified PVC‐P are more consistent in processing and achieve reproducible surface characteristics. Based on this study, a novel “anchor modification” was proposed regarding CICs modified surface. This “anchor modification” is likely to reduce plasticizer extraction from PVC‐P and also can be utilized for the modification of polymers other than PVC‐P. © 2008 Wiley Periodicals, Inc. J Biomed Mater Res, 2009
The mechanism of deposition of calcium phosphate coatings from solution onto magnesium alloy AZ31
Authors: Gray‐Munro J. E. , Strong M.
Published: May 2008

In recent years, magnesium alloys have been proposed as a new class of metallic bioabsorbable implant material. Unfortunately, hydrogen gas evolution and an increase in alkalinity are both byproducts of the degradation process. This necessitates the development of magnesium alloys with controlled degradation rates. The development of biocompatible coatings that can delay the onset of corrosion is essential for improving the lifetime and performance of these materials in vivo. Calcium phosphate coatings have been shown to improve the biocompatibility of metallic implants for orthopedic applications. In this article, we report a solution chemistry technique for depositing calcium phosphate coatings on magnesium alloy surfaces. Our kinetic studies indicate that the deposition of the coating is related to the anodic dissolution of the substrate. Characterization of the coating by XPS, SEM/EDS, and XRD reveal that the coating produced is a poorly crystalline calcium magnesium hydroxyapatite material. © 2008 Wiley Periodicals, Inc. J Biomed Mater Res, 2009
Multiaxial analysis of dental composite materials
Authors: Kotche Miiri , Drummond James L. , Sun Kang , Vural Murat , DeCarlo Francesco
Published: May 2008

Dental composites are subjected to extreme chemical and mechanical conditions in the oral environment, contributing to the degradation and ultimate failure of the material in vivo. The objective of this study is to validate an alternative method of mechanically loading dental composite materials. Confined compression testing more closely represents the complex loading that dental restorations experience in the oral cavity. Dental composites, a nanofilled and a hybrid microfilled, were prepared as cylindrical specimens, light‐cured in ring molds of 6061 aluminum, with the ends polished to ensure parallel surfaces. The samples were subjected to confined compression loading to 3, 6, 9, 12, and 15% axial strain. Upon loading, the ring constrains radial expansion of the specimen, generating confinement stresses. A strain gage placed on the outer wall of the aluminum confining ring records hoop strain. Assuming plane stress conditions, the confining stress (σc) can be calculated at the sample/ring interface. Following mechanical loading, tomographic data was generated using a high‐resolution microtomography system developed at beamline 2‐BM of the Advanced Photon Source at Argonne National Laboratory. Extraction of the crack and void surfaces present in the material bulk is numerically represented as crack edge/volume (CE/V), and calculated as a fraction of total specimen volume. Initial results indicate that as the strain level increases the CE/V increases. Analysis of the composite specimens under different mechanical loads suggests that microtomography is a useful tool for three‐dimensional evaluation of dental composite fracture surfaces. © 2008 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2009
Effects of geometry on fracture initiation and propagation in all‐ceramic crowns
Authors: Rekow E. Dianne , Zhang Guangming , Thompson Van , Kim Jae‐Won , Coehlo Paulo , Zhang Yu
Published: May 2008

The complex and patient‐unique geometry of posterior all‐ceramic dental crowns represents a particularly interesting set of challenges to understanding stress concentration and fracture evolution in response to loading. A series of numerical and physical experiments, with both single cycle and fatigue loading, show that geometry profoundly influences the stress concentration and fracture initiation and propagation. In stylized crowns with uniform axial wall height, stresses concentrate beneath the indenter. As the height of the axial wall increases, loads to cause failure increase linearly. In crowns with variation in axial wall height around the periphery, stresses concentrate both beneath the indenter and at the margin of the core ceramic. The magnitude of the stress concentration at the margin is directly related to the amount of variation in axial wall height around the periphery of the crown. Anatomically correct veneered zirconia core crowns subjected to single‐cycle loads, fracture in areas of greatest stress concentration identified by finite element models. Fractures and stress concentrations that occur in response to single‐cycle loading are important indicators of initiation sites for fatigue failure. © 2008 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2009
Analysis of the fracture morphology of polyamide, polyester, polypropylene, and silk sutures before and after implantation in vivo
Authors: Karaca Esra , Hockenberger Asli S.
Published: May 2008

This study has analyzed fracture morphology of four nonabsorbable commercially available sutures before and after implantation in rats. Also, tensile and knot strength retention have been evaluated after 3 and 8 weeks in vivo. Scanning electron and optical light microscopes were used for analysis of fracture morphologies and surface changes of the sutures. A clear effect of in vivo on the tensile and knot strength changes, and the fracture mechanism was seen for braided sutures. The suture size was also important for braided sutures, as fibrous tissue formation plays an important role in terms of the size. The fiber's surface properties were also important for the fracture morphology. A smooth and even surface was not suitable for the fibrous tissue formation as seen in monofilament sutures. Therefore, the polymer type was very important for the monofilament sutures, as it was the most important parameter to determine the fracture morphology and was not affected by the implantation and the implantation time. The size of the suture was also important for the polypropylene in terms of axial splitting before and after implantation. This, however, was not the case for knot strength tests. The knot was undone regardless of the size. Surface characteristics were very important for braided sutures, as they have a rough surface that supports tissue formation on the fracture mechanism, tensile and knot strength. Silk suture has single filaments with no regular diameter and smooth surface. Therefore, silk suture has more tissue formation postimplantation compared to polyester suture. © 2008 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 2008
Effects of environmental calcium and phosphate on wear and strength of glass ionomers exposed to acidic conditions
Authors: Wang X. Y. , Yap Adrian U. J.
Published: May 2008

This study evaluated the effects of environmental calcium and phosphate on wear resistance, strength, and surface morphology of highly viscous glass‐ionomers (HVGICs) (Fuji IX Fast [FN] and KetacMolar [KM]) when exposed to acidic conditions. Fabricated specimens were randomly divided into five groups and kept in acidic solutions (pH 3) with varied levels of calcium and phosphate ranging from 0 to 2.4 mM. After 4 weeks of conditioning, the specimens were subjected to wear testing, shear punch, and surface roughness testing as well as SEM evaluation. Multiple comparisons of wear depth (μm), shear strength (MPa), and surface roughness (Ra) between acidic conditions were performed using ANOVA/post‐hoc Scheffe's test (p < 0.05). Results showed that FN and KM exposed to acidic conditions had varied wear resistance, shear strength, surface roughness, and structure depending on environmental phosphate level. Increased level of environmental phosphate led to rougher surface, greater wear resistance, and strength of FN and KM than the controls (acid of pH 3). Under SEM, the surface of both FN and KM specimens were covered by numerous small particles when environmental phosphate was high. Results suggest that environmental phosphate may improve wear resistance and shear strength of HVGICs when challenged by acids. © 2008 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2009
ABSINTH: A new continuum solvation model for simulations of polypeptides in aqueous solutions
Authors: Vitalis Andreas , Pappu Rohit V.
Published: May 2008

A new implicit solvation model for use in Monte Carlo simulations of polypeptides is introduced. The model is termed ABSINTH for self‐Assembly of Biomolecules Studied by an Implicit, Novel, and Tunable Hamiltonian. It is designed primarily for simulating conformational equilibria and oligomerization reactions of intrinsically disordered proteins in aqueous solutions. The paradigm for ABSINTH is conceptually similar to the EEF1 model of Lazaridis and Karplus (Proteins 1999, 35, 133). In ABSINTH, the transfer of a polypeptide solute from the gas phase into a continuum solvent is the sum of a direct mean field interaction (DMFI), and a term to model the screening of polar interactions. Polypeptide solutes are decomposed into a set of distinct solvation groups. The DMFI is a sum of contributions from each of the solvation groups, which are analogs of model compounds. Continuum‐mediated screening of electrostatic interactions is achieved using a framework similar to the one used for the DMFI. Promising results are shown for a set of test cases. These include the calculation of NMR coupling constants for short peptides, the assessment of the thermal stability of two small proteins, reversible folding of both an α‐helix and a β‐hairpin forming peptide, and the polymeric properties of intrinsically disordered polyglutamine peptides of varying lengths. The tests reveal that the computational expense for simulations with the ABSINTH implicit solvation model increase by a factor that is in the range of 2.5–5.0 with respect to gas‐phase calculations. © 2008 Wiley Periodicals, Inc. J Comput Chem, 2009
On relativistic effects in ground state potential curves of Zn2, Cd2, and Hg2 dimers. A CCSD(T) study
Authors: Bučinský Lukáš , Biskupič Stanislav , Ilčin Michal , Lukeš Vladimír , Laurinc Viliam
Published: May 2008

The ground state potential curves of the Zn2, Cd2, and Hg2 dimers calculated at different levels of theory are presented and compared with each other as well as with experimental and other theoretical studies. The calculations at the level of Dirac‐Coulomb Hamiltonian (DCH), 4‐component spin‐free Hamiltonian, nonrelativistic Lévy–Leblond Hamiltonian and at the level of simple Coulombic correction to DCH are presented. The potential curves are calculated in an all‐electron supermolecular approach including the correction to basis set superposition error (BSSE). Electron correlation is treated at the coupled cluster level including single and double excitations and noniterative triple corrections, CCSD(T). In addition, simulations of the temperature dependence of dynamic viscosities in the low‐density limit using the obtained ground state potential curves are presented. © 2008 Wiley Periodicals, Inc. J Comput Chem, 2009
Regulation of insulin receptor substrate‐1 expression levels by caveolin‐1
Authors: Chen Jia , Capozza Franco , Wu An , deAngelis Tiziana , Sun Hongzhi , Lisanti Michael , Baserga Renato
Published: May 2008

The insulin receptor substrate‐1 (IRS‐1), a docking protein of the type 1 insulin‐like growth factor receptor (IGF‐IR) plays a significant role in cell proliferation and differentiation. The expression of IRS‐1 is down‐regulated in mouse embryo fibroblasts (MEFs) with a deletion of caveolin‐1 (cav1) genes (KO cells). Levels of IRS‐1 mRNA are not affected. Re‐introduction of cav1 into KO cells rescues IRS‐1 expression. Stabilization of protein levels is reciprocal and a strict correlation between IRS‐1 and cav1 levels was confirmed in five cell lines, and in mouse tissues. IRS‐1 binds through its phosphotyrosine binding (PTB) domain to tyrosine 14 (Y14) of cav1, the residue phosphorylated by IGF‐1 stimulation and by v‐src. The down‐regulation of IRS‐1 in cav−/− cells occurs via the proteasome pathway. These results indicate a novel mechanism for the regulation of IRS‐1 expression levels, an important finding in view of IRS‐1 role in cell proliferation and transformation. J. Cell. Physiol. 217: 281–289, 2008. © 2008 Wiley‐Liss, Inc.
Artificial neural networks model for the prediction of steady state phenol biodegradation in a pulsed plate bioreactor
Authors: Shetty K Vidya , Nandennavar Santosh , Srinikethan G
Published: May 2008

BACKGROUND: A recent innovation in fixed film bioreactors is the pulsed plate bioreactor (PPBR) with immobilized cells. The successful development of a theoretical model for this reactor relies on the knowledge of several parameters, which may vary with the process conditions. It may also be a time‐consuming and costly task because of their nonlinear nature. Artificial neural networks (ANN) offer the potential of a generic approach to the modeling of nonlinear systems.

RESULTS: A feedforward ANN based model for the prediction of steady state percentage degradation of phenol in a PPBR by immobilized cells of Nocardia hydrocarbonoxydans (NCIM 2386) during continuous biodegradation has been developed to correlate the steady state percentage degradation with the flow rate, influent phenol concentration and vibrational velocity (amplitude × frequency). The model used two hidden layers and 53 parameters (weights and biases). The network model was then compared with a Multiple Regression Analysis (MRA) model, derived from the same training data. Further these two models were used to predict the percentage degradation of phenol for blind test data.

CONCLUSIONS: The performance of the ANN model was superior to that of the MRA model and was found to be an efficient data‐driven tool to predict the performance of a PPBR for phenol biodegradation. Copyright © 2008 Society of Chemical Industry