bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification of antigen‐specific B cells by concurrent monitoring of intracellular Ca2+ mobilization and antigen binding with microwell array chip system equipped with a CCD imager
Authors: Kinoshita Koshi , Ozawa Tatsuhiko , Tajiri Kazuto , Kadowaki Shinichi , Kishi Hiroyuki , Muraguchi Atsushi
Published: June 2009

B cells are very heterogeneous, consisting of more than 109 B‐cell clones with distinct specificities for antigens in each individual. To identify single B cells with antigen specificity, we have been developing cell microarray technology using microwell array chips whose microwells each capture a single B cell. Using microwell array chips, we detected antigen‐specific B cells by monitoring antigen‐induced intracellular Ca2+ mobilization with a CCD scanner (MAC‐CCD system) or the binding of fluorescence‐labeled antigen to cells with a confocal laser scanner. We retrieved target cells from the chip, cloned immunoglobulin genes, and produced antigen‐specific antibodies. However, these methods present some difficulties: the former technique could not detect cells whose frequency was less than 0.05% and the latter one took a long time to identify the objective cells although it could detect cells at a frequency of 0.01%. Here, we have combined the advantages of these two methods. Monitoring antigen‐induced intracellular Ca2+ mobilizations and the binding of fluorescence‐labeled antigens simultaneously with a MAC‐CCD system enabled us to detect rapidly, antigen‐specific B cells whose frequency was less than 0.01% with high efficiency. Our system provides a superior screening system for antigen‐specific B cells and extends the horizons of multiparameter single‐cell analysis in heterogeneous cell populations. © 2009 International Society for Advancement of Cytometry
A comparative analysis of fine‐needle capillary cytology vs. fine‐needle aspiration cytology in superficial lymph node lesions
Authors: Sajeev Suraj , Siddaraju Neelaiah
Published: June 2009

Fine‐needle capillary cytology (FNCC) has been attempted in various organs and studies have shown this procedure to yield qualitatively superior material compared with fine‐needle aspiration cytology (FNAC). Studies evaluating the efficacy of this technique in lymph nodes are rare. The present study has attempted to assess the relative advantages and disadvantages of the FNCC technique in comparison to the more widely applied FNAC technique.

Thirty enlarged lymph nodes from 26 patients were sampled by both the FNCC and FNAC techniques. The smears obtained were routinely stained by May–Grünwald–Giemsa (MGG) and Papanicolaou staining. The quality of smears was evaluated using an objective scoring system originally devised by Mair et al., for various organs. The score of individual parameters in each case as well as the total scores for FNAC and FNCC procedures were calculated separately and Mann‐Whitney's test was performed; a P‐value of less than 0.05 was considered significant. Statistical results showed smears obtained by FNCC to be qualitatively better than those obtained by FNAC. Though, individual parameters were not statistically significant, FNCC smears showed better scores as compared with those of FNA smears. Also, the technique was found to be easier to perform and less apprehensive to the patient.

Our study convincingly proved the technical superiority of the FNCC technique in cellular lymph node lesions, emphasizing the need for this less publicized procedure to be more widely applied. Diagn. Cytopathol. 2009. © 2009 Wiley‐Liss, Inc.
Strongyloides stercoralis in a bronchial washing specimen processed as conventional and Thin‐Prep smears: Report of a case and a review of the literature
Authors: Grapsa Dimitra , Petrakakou Efthalia , Botsoli‐Stergiou Efi , Mikou Panagiota , Athanassiadou Pauline , Karkampasi Athina , Ioakim‐Liossi Anna
Published: June 2009

Strongyloidiasis is an opportunistic infection which may result in a fatal hyperinfection syndrome in immunocompromised patients. We report the case of a pulmonary infection with Strongyloides stercoralis in a 61‐year‐old male with a history of a long‐term administration of corticosteroids. Cytologic examination of a bronchial washing specimen, processed both as conventional and as Thin‐Prep smears, revealed an abundance of the typical larvae of Strongyloides stercoralis, amidst a cellular population comprising several acute inflammatory cells as well as bronchial epithelial cells with features of basal cell hyperplasia or regenerative atypia. To the best of our knowledge there is only one previous report describing Strongyloides stercoralis in thin‐layer smears, and there are no previous studies comparing its morphology in conventional and thin‐layer preparations. Diagn. Cytopathol. 2009. © 2009 Wiley‐Liss, Inc.
Developing medical countermeasures: from BioShield to BARDA
Authors: Tucker Jonathan B.
Published: June 2009

The U.S. Congress passed the Project BioShield Act in 2004 to create market incentives for the private sector to develop medical countermeasures (MCMs) against high‐priority chemical, biological, radiological, and nuclear threats. Two years later, Congress patched recognized gaps in the BioShield legislation by adopting the Pandemic and All‐Hazards Preparedness Act of 2006, which established the Biomedical Advanced Research and Development Authority (BARDA) within the Department of Health and Human Services (DHHS). BARDA provides financial and managerial support for companies developing MCMs. This article examines U.S. government efforts in the MCM field and prospects for the future. Drug Dev Res 70:224–233, 2009. © 2009 Wiley‐Liss, Inc.
Developing technologies in biodefense research: computational drug design
Authors: Clark Matthew , Meshkat Sia , Talbot George , Konteatis Zenon , Ludington Jennifer , Zou Jinming , Freedman Steven J. , Wiseman Jeffrey S.
Published: June 2009

The development of small‐molecule drugs to counter the threat of bioterrorism will differ from classical drug discovery because it will be impossible to evaluate efficacy in clinical trials for many agents. This difference focuses biodefense on the identification of multiple drug candidates for each threat organism so that multiple treatments can be mounted simultaneously when needed to maximize the probability of success. Accordingly, drug discovery will become the rate‐ and cost‐limiting phase of the overall drug development process. We address the potential of computational chemistry to optimize efficiency and efficacy in the discovery phase. The major elements required for a successful computational approach are the calculation of binding free energy, accounting for changes in solvation on ligand binding, and compensating for protein flexibility. Drug Dev Res 70:279–287, 2009. © 2009 Wiley‐Liss, Inc.
Smart planner: radically accelerating R&D to combat a biothreat
Authors: Chadwick Andrew T. , Edwards Roger A.
Published: June 2009

Conventional R&D processes are ill‐suited to biothreats and biothreat preparation because they are intended to support risk‐averse decisions for patients and are designed for longer expected development times. The Smart Planner tool is a risk visualization framework developed to help contingency and R&D planners quantify and balance risk, uncertainty, and time. The tool incorporates the following capabilities: (1) visualization of the risks of inaction; (2) identification of critical areas of uncertainty where new information can really make a difference; (3) decision support for (i) development and treatment options and (ii) optimization of tradeoffs given various timescales. The tool facilitates alignment of research planners' acceptance of risks with policy‐makers' strategic views of benefits in the context of apparent or overt threats. Policy and ethical implications for application of the tool are also discussed. Drug Dev Res 70:335–348, 2009. © 2009 Wiley‐Liss, Inc.
Perception of overweight and self‐esteem during adolescence
Authors: Perrin Eliana M. , Boone‐Heinonen Janne , Field Alison E. , Coyne‐Beasley Tamera , Gordon‐Larsen Penny
Published: June 2009

Objective:

To examine sex‐ and race/ethnicity‐specific relationships between adolescents' self‐esteem and weight perception.

Method:

Descriptive analysis and logistic regression of Wave II of the National Longitudinal Study of Adolescent Health (N = 6,427 males, 6,574 females; ages 11–21) examined associations between low self‐esteem and perceived overweight within body mass index (BMI) percentile categories, controlling for sociodemographics and stratified by sex and race/ethnicity.

Results:

25.1% and 8% of normal weight females and males, respectively, perceived themselves as overweight, with variation by race/ethnicity. Low self‐esteem was most strongly associated with misperceived overweight in moderate BMI percentile categories (males: OR = 2.34; 95% CI: 1.60–3.41; females: OR = 2.39; 95% CI: 1.82, 3.16). Odds of correctly perceived overweight were higher for low (versus high) self‐esteem in white and black females but not males of any race/ethnicity.

Discussion:

Understanding subgroup differences by race/ethnicity in perceived overweight‐self‐esteem relationships may inform eating disorders' prevention strategies. © 2009 by Wiley Periodicals, Inc. Int J Eat Disord 2010
The Passerini Reaction with CF3‐Carbonyl Compounds – Multicomponent Approach to Trifluoromethyl Depsipeptides
Authors: Gulevich Anton V. , Shpilevaya Inga V. , Nenajdenko Valentine G.
Published: June 2009

The first detailed investigation of the Paserini reaction with CF3‐carbonyl compounds is reported. The reaction provides a new approach to trifluorolactic acid derivatives and CF3‐substituted depsipeptides. The method is promising for the synthesis of chiral trifluoromethyl depsipeptides, i.e. orthogonally protected building blocks for incorporation into naturally occurring depsipeptides.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)
Enantiomerically Pure Vinylcyclopropylboronic Esters
Authors: Hohn Erwin , Paleček Jiří , Pietruszka Jörg , Frey Wolfgang
Published: June 2009

Vinylcyclopropanes are versatile intermediates and products in organic synthesis. The corresponding enantiomerically pure boronic esters should lead to highly flexible building blocks with a variety of applications. A detailed study towards the selective synthesis of (E)‐ and (Z)‐vinyl derivatives starting from the known diastereo‐ and enantiopure cyclopropylmethanols 3 and 4 is presented. The boronic esters were activated via their trifluoroboronates; the optimization of the reaction is discussed. The endeavour culminated in the synthesis of (–)‐(1S,2S)‐dictyopterene A (38). (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)
Salt karst and tectonics: sinkholes development along tension cracks between parallel strike‐slip faults, Dead Sea, Jordan
Authors: Closson Damien , Karaki Najib Abou
Published: June 2009

This work deals with the tectonic interpretation of an alignment of more than 300 sinkholes stretching along the Jordanian coast of the Dead Sea, Ghor Al Haditha area. Its dimensions are 6 km long with a width of 600 m. Sinkholes appeared during the last decades as a consequence of the very rapid lowering of the lake level. The linear shape was inferred from ground collapse inventories carried out between 1991 and 2008. The lineament is replaced and analyzed in its structural setting at regional and local scales. Its direction (N 24° E) is sub‐parallel to the ones displayed by many focal mechanisms, especially the one associated with the earthquake of the 23 April, 1979 (mb = 5·1; N 20° E ± 5°), which is representative of all focal mechanisms calculated on a fault plane compatible with the general direction of the Jordan‐Dead Sea Transform fault system for the east coast of the Dead Sea area.

The alignment of sinkholes is constituted by 13 minor linear segments separated by as many empty spaces. Four minor linear units present an en‐echelon arrangement from which one can deduce the presence of a local extensional stress field. In this context, the sinkhole locations provide information of subsurface discontinuities interpreted as hidden fractures. In a close future, such results could support the work of decision‐makers and engineers in the projected development of the area. Copyright © 2009 John Wiley & Sons, Ltd.
Preparation and Characterisation of Pelletised Glass Electrolytes for Fuel Cells
Authors: Nogami M. , Tanaka K. , Uma T.
Published: June 2009

This paper reports on the preparation and characterisation of pelletised glass electrolytes that were fabricated with a proton conducting glass derived from a sol–gel technique, and several kinds of binders. The electrolytes, consisting of a glass powder that had been pulverised by planetary ball milling and mixed with an orthophosphoric acid binder, gave rise to a maximum proton conductivity of 1.3 × 10–2 S cm–1 measured at 80 °C and 80% relative humidity. The pore diameter of the PGE was in this case ∼2 nm. The hydrogen gas permeability was analysed as a function of the temperature and was found to be on the order of 10–10 mol cm–1 s–1 Pa–1 at 100 °C. Current–voltage measurements were carried out at room temperature using the PGE under H2 and O2 flow. Power densities were obtained from the I–V curves during fuel cell operation at 80 °C and 100% R.H.
Acheulean artifact accumulation and early hominin land use, Garden Route Casino Road, Pinnacle Point, South Africa
Authors: Thompson Erin
Published: June 2009

An Early Stone Age Acheulean lithic assemblage collected along a 1.5‐km transect at the Garden Route Casino near Pinnacle Point, Mossel Bay, South Africa, was examined in order to assess the relative degree to which assemblage variability is impacted by post‐occupational processes and/or terrain. It was found that post‐occupational variables do vary across the study area, and they affect the positions of artifacts to different degrees. Terrain structure was determined to have minimal effect on artifact movement. Three analysis sections were identified as having artifacts that were likely close to their original positions and compositions. Future interpretations of differential land use can now be tempered with considerations of the post‐occupational processes that formed the recovered assemblage. © 2009 Wiley Periodicals, Inc.
Analysis of potential direct insolation as a degradation factor of cave paintings in Villar del Humo, Cuenca, Central Spain
Authors: Díez‐Herrero Andres , Gutiérrez‐Pérez Ignacio , Lario Javier , Cañaveras Juan C. , Benavente David , Sánchez‐Moral Sergio , Alonso‐Azcárate Jacinto
Published: June 2009

The purpose of this study is to assess the impact of direct sunlight on eleven given points of interest in Villar del Humo (Cuenca, Central Spain), and to determine to what extent this direct insolation, which is affected by both the regional and the local geomorphological configuration, influences the state and type of degradation of the paintings or of the host rock. The analysis of potential direct insolation with geographical information system (GIS) tools and morphometric field measurements shows that in latitudes such as the ones studied in this case, not only insolation time but also the maximum angle of solar elevation above the horizon seem to be of relevance when it comes to determining the influence of direct insolation. We believe this to be useful information, in particular with regard to the management and preservation of this archaeological heritage, declared a UNESCO World Heritage Site. © 2009 Wiley Periodicals, Inc.
HRD as a profession: Current status and future directions
Authors: Kahnweiler William M.
Published: June 2009

Where does HRD stand as a bona fide profession? Where does it need to go in the future in its quest to become an established and widely recognized profession? What short‐ and long‐range strategies are needed to get it there? What issues and challenges need to be addressed that will enable HRD to continue evolving, growing, and advancing as a profession? This article is an attempt to begin addressing these critical and complex questions. An assessment of where HRD currently stands as a profession and two potential strategies that might assist HRD to elevate its professional stature are offered.
The effect of learning organization culture on the relationship between interpersonal trust and organizational commitment
Authors: Song Ji Hoon , Kim Hong Min , Kolb Judith A.
Published: June 2009

The primary purpose of this research was to assess the effect of learning organization culture on the linkage between interpersonal trust and organizational commitment. The study sample was obtained from employees of two major Korean conglomerates. Online questionnaires were completed by 321 respondents. Structural equation modeling (SEM) was used to detect the effects of learning organization culture on the basis of the model fit to data comparisons and the significance of path coefficient estimates in the hypothesized model. The results suggest that learning organization culture works as a mediating variable to explain the association between interpersonal trust and organizational commitment. Recommendations for future research and implications for human resource development research and practice are discussed.
Toward development of a generalized instrument to measure andragogy
Authors: Holton Elwood F. , Wilson Lynda Swanson , Bates Reid A.
Published: June 2009

Andragogy has emerged as one of the dominant frameworks for teaching adults during the past 40 years. A major and glaring gap in andragogy research is the lack of a measurement instrument that adequately measures both andragogical principles and process design elements. As a result, no definitive empirical test of the theory has been possible. The purpose of this article is to report on initial attempts to develop a survey instrument that corrects this shortcoming in the andragogy research literature. The instrument developed for this study was part of a comprehensive examination of andragogical principles and process design elements and their effect on student satisfaction and learning outcomes in a postsecondary education setting. It was administered to 404 adults enrolled in an adult‐oriented postgraduate degree program. Exploratory factor analysis revealed promising scales to measure five of the six andragogical principles and six of the eight process design elements. This instrument is the most successful attempt to date to measure andragogical principles and elements. It holds promise for advancing research on andragogy, and subsequently advancing the field of HRD by explaining affective and cognitive responses to andragogical instructional strategies across a spectrum of learning environments. Additional implications for future research to strengthen the instrument are also discussed.
Effects of topography on the spatial distribution of evapotranspiration over a complex terrain using two‐source energy balance model with ASTER data
Authors: Kafle H. K. , Yamaguchi Y.
Published: June 2009

Spatial distribution of evapotranspiration (ET) over a complex terrain is estimated using a new approach of the conventional two‐source energy balance (TSEB) model by considering the effect of topography (difference in slope and aspect). We name this approach topography considered two‐source energy balance (T2SEB) model. The novelty of this model is the estimation of incoming shortwave solar radiation considering slope, aspect, altitude, latitude, longitude, and the day of calculation in the TSEB model, so that the new model should have wider applicability than existing models over topographically complex areas. In this study, high spatial resolution Advanced Spaceborne Thermal Emission and Reflection Radiometer (ASTER) data and meteorological data are used. ET over a complex terrain of Nagoya, Japan, on three different dates, 4 November 2005, 25 May 2004 and 30 October 2003, is estimated using both TSEB and T2SEB models. To validate both models, estimated results are compared with ground observation data at the flux tower site. Moreover, estimated results from TSEB and T2SEB models are compared in five different locations of different topography within the study area. Variation of net radiation absorbed by the surface (Rn) with topographical variables is also studied with the help of scatter plots. Estimated results for all three dates agreed within ±75 W m−2 with calculated values from both models at the flux tower site. TSEB underestimated/overestimated ET in sunlit/shaded areas in hilly areas. The T2SEB model estimated ET in hilly areas better than the TSEB model. Copyright © 2009 John Wiley & Sons, Ltd.
Impact of stem water storage on diurnal estimates of whole‐tree transpiration and canopy conductance from sap flow measurements in Japanese cedar and Japanese cypress trees
Authors: Kumagai Tomo'omi , Aoki Sayaka , Otsuki Kyoichi , Utsumi Yasuhiro
Published: June 2009

The amount of water stored in the stem introduces uncertainty when estimating diurnal whole‐tree transpiration (ET) and canopy stomatal conductance (GC) using sap flow measured at the base of the stem (Q). Thus, to examine how ET can be calculated from Q, we obtained ET using sap flow and stem water content measurements and a whole‐tree water balance equation, and compared it with Q. In this study, we measured sap flows in 33‐year‐old individual trees of Cryptomeria japonica D. Don and Chamaecyparis obtusa Endl. using constant‐heat sap flow probes. Sap flows were measured at several depths at the base of the stem, and at the upper trunk as a surrogate of ET. Stem water contents were measured at three vertical positions on the trunk using amplitude‐domain reflectometry (ADR) sensors. We also measured sapwood volumes of the study trees. Using simultaneous sap flow and stem water content measurements along the tree stem, we confirmed that stem water storage has impacts on the transpiration stream. These include sap flow lags along the tree heights and an enhanced peak of transpiration from stem sap flow. These results enabled us to calculate the correct ET by multiplying Q by 1·18 and shifting its time series forward by 30 min. The ET value was then used to calculate GC for both tree species. The factor of 1·18 is based on the fact that at noon, the value of ET was higher than that of Q, due to the prolonged Q during the evening. Establishing the time lag was relatively simple and was determined by comparing Q and vapor pressure deficit. The multiplier is more challenging to ascertain due to the difficulty in obtaining ET correctly. Copyright © 2009 John Wiley & Sons, Ltd.
The sulphur isotope and hydrochemical characteristics of Skeiðarársandur, Iceland: identification of solute sources and implications for weathering processes
Authors: Robinson Zoe P. , Fairchild Ian J. , Spiro Baruch
Published: June 2009

The hydrochemistry of sulphur in the active outwash plain of Skeiðarársandur, SE Iceland shows considerable variety reflecting differences in sources and processes, and is investigated in this article using δ34S values of dissolved sulphate and igneous sulphide minerals, δ18OH2O, and ionic concentrations in waters. Seawater‐derived sulphate is a notable component only in the lower sandur (δ34SSO4 = +6·8‰ VCDT). δ34SSO4 in the Skeiðará glacial melt river range from +3·4 to +8·8‰δ34S. The higher values occur during a flood event and reflect geothermal sulphate contributions from the Grímsvötn caldera. ‘Kettle‐hole lakes’ formed since the November 1996 jökulhlaup form important ecological niches and show evidence of coupled sulphide oxidation and carbonate and possibly silicate dissolution and have the lowest δ34SSO4 values (average −0·8‰) attributed to higher proportions of sulphide oxidation‐derived SO42− and/or bacterially mediated sulphide oxidation. The hydrochemistry of eastern sandur groundwater is influenced by a hydrothermal source of reduced sulphur from the Grímsvötn caldera or a localized area of geothermal springs, and contrasts with the hydrochemistry of the majority of groundwaters and the Sulá and Gígjukvísl rivers in western and central Skeiðarársandur. These have lower [Ca2+ + Mg2+], [Na+ + K+] and SO42− concentrations and δ34S values consistent with sulphate derived from the oxidation of igneous sulphides. In comparison to catchments dominated by atmospherically transported sulphate, catchments such as this where the sulphur system is dominated by internal sources (rock‐derived and geothermal) will not be sensitive to the temporal decreasing trends in contributions from long‐range airborne sulphate resulting from reductions of sulphur emissions in North America and Europe. Copyright © 2009 John Wiley & Sons, Ltd.
Functional impact of sequence variation in the promoter region of TGFB1
Authors: Healy Jasmine , Dionne Joëlle , Bélanger Hélène , Larivière Mathieu , Beaulieu Patrick , Labuda Damian , Sinnett Daniel
Published: June 2009

Pathological deregulation of the transforming growth factor, beta 1 (TGFB1) pathway has been implicated in the development of several major diseases, including cancers. Regulatory variation in the TGFB1 gene may lead to altered TGFB1 expression and activity, and thus, modulate an individual's susceptibility to disease. Here, we performed a study of the functional relevance of cis‐acting regulatory variation in the proximal promoter region of the TGFB1 gene. In a previous study, 9 promoter polymorphisms were identified in the 2kb region upstream of the transcription start site and 9 distinct promoter haplotypes were inferred from a panel of individuals from 5 distinct continental population groups. Following experimental validation, we found that the 2 major haplotypes significantly influenced TGFB1 transcriptional activity in an allele‐specific manner and that 3 of the SNPs (−1886G>A, −509C>T and −1550DEL/AGG) altered DNA‐protein complexe formation. Though the biological relevance of these findings remains to be verified, our study suggests that polymorphisms in the TGFB1 promoter could indeed influence gene expression and potentially contribute to the pathogenesis of TGFB1 related diseases. © 2009 UICC
The dual EGFR/HER‐2 tyrosine kinase inhibitor lapatinib sensitizes colon and gastric cancer cells to the irinotecan active metabolite SN‐38
Authors: LaBonte Melissa J. , Manegold Philipp C. , Wilson Peter M. , Fazzone Will , Louie Stan G. , Lenz Heinz‐Josef , Ladner Robert D.
Published: June 2009

Members of the human epidermal receptor (HER) family are frequently associated with aggressive disease and poor prognosis in multiple malignancies. Lapatinib is a dual tyrosine kinase inhibitor targeting the epidermal growth factor receptor (EGFR) and HER‐2. This study evaluated the therapeutic potential of lapatinib, alone and in combination with SN‐38, the active metabolite of irinotecan (CPT‐11), in colon and gastric cancer cell lines. Concentration‐dependent antiproliferative effects of both lapatinib and SN‐38 were observed in all colon and gastric cancer cell lines tested but varied significantly between individual cell lines (lapatinib range 0.08–11.7 μM; SN‐38 range 3.6–256 nM). Lapatinib potently inhibited the growth of a HER‐2 overexpressing gastric cancer cell line and demonstrated moderate activity in gastric and colon cancer cells with detectable HER‐2 expression. The combination of lapatinib and SN‐38 interacted synergistically to inhibit cell proliferation in all colon and gastric cancer cell lines tested. Cotreatment with lapatinib and SN‐38 also resulted in enhanced cell cycle arrest and the induction of apoptosis with subsequent cellular pharmacokinetic analysis demonstrating that lapatinib promoted the increased intracellular accumulation and retention of SN‐38 when compared to SN‐38 treatment alone. Finally, the combination of lapatinib and CPT‐11 demonstrated synergistic antitumor efficacy in the LoVo colon cancer mouse xenograft model with no apparent increase in toxicity compared to CPT‐11 monotherapy. These results provide compelling preclinical rationale indicating lapatinib to be a potentially efficacious chemotherapeutic combination partner for irinotecan in the treatment of gastrointestinal carcinomas. © 2009 UICC
Antitumor activity of delimotecan against human metastatic melanoma: Pharmacokinetics and molecular determinants
Authors: Bigioni Mario , Parlani Massimo , Bressan Alessandro , Bellarosa Daniela , Rivoltini Licia , Animati Fabio , Crea Attilio , Bugianesi Rossana , Maggi Carlo Alberto , Manzini Stefano , Binaschi Monica
Published: June 2009

Delimotecan (MEN 4901/T‐0128) is a new cytotoxic prodrug constituted by a camptothecin analog (T‐2513) bound to carboxymethyl dextran through a triglycine linker. A significant antitumor activity of delimotecan against human metastatic melanoma xenograft model Me15392 is reported. Dacarbazine, the drug approved for the treatment of metastatic melanoma, was ineffective in this melanoma model. Pharmacokinetic studies, together with the expression analysis of mRNA for enzymes involved in delimotecan metabolism, showed that T‐2513 and other cytotoxic metabolites of delimotecan (SN 38 and T‐0055) are generated in greater quantities in the tumor tissue than in toxicity target tissues, such as liver, thus accounting for the antitumoral activity. Moreover, we demonstrated that human metastatic melanoma cells are able to phagocytose delimotecan and cleave it to release the cytotoxic moieties T‐2513 in the tumoral environment. Further flow cytometric analysis showed a higher recruitment of macrophages in xenografted human metastatic melanoma, when compared with other human tumors. Thus, the antitumoral activity of delimotecan exerted on metastatic melanoma is due to several factors: (i) the ability of melanoma cells to phagocytose and metabolise delimotecan; (ii) the accumulation of delimotecan in tumoral mass; (iii) the recruitment of macrophage cells to the melanoma nodule and (iv) the expression in melanoma cells of a pattern of enzymes that converts delimotecan into cytotoxic metabolites. Based on these results, delimotecan might be exploited as a new anticancer agent for the therapy of metastatic melanoma because of its high efficacy and good selectivity, and therefore clinical trials for this indication are warranted. © 2009 UICC
Histogram‐based filtering for quantitative 3D retinal angiography
Authors: Kolbitsch Christoph , Schmoll Tilman , Leitgeb Rainer A.
Published: June 2009

Doppler Fourier domain optical coherence tomography (D‐FDOCT) can be used to visualise and measure ocular blood flow in the retina of the human eye. This has the potential to diagnose illnesses such as macula degeneration or diabetic retinopathy early on because these medical conditions cause a pathological change in the retinal vasculature and perfusion. Here we are presenting a method to separate quantitative blood flow information from static tissue. Our approach is demonstrated on retinal D‐FDOCT volume scans taken at the optic nerve head (see figure) and near the fovea with a high speed CMOS‐based FDOCT system. The advantage of this method is the small post‐processing effort together with the immediate availability of segmented quantitative Doppler flow maps. The performance of the filtering technique is also compared to spatial frequency filtering methods. (© 2009 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Study of the electrospun PLA/silk fibroin‐gelatin composite nanofibrous scaffold for tissue engineering
Authors: Gui‐Bo Yin , You‐Zhu Zhang , Shu‐Dong Wang , De‐Bing Shi , Zhi‐Hui Dong , Wei‐Guo Fu
Published: June 2009

In this article, a nanofibrous composite scaffold of poly L‐lactic acid(PLA)/silk fibroin(SF)‐gelatin was fabricated by multilayer electrospinning. To investigate the feasibility of PLA/SF‐gelatin use as scaffolds, the porosity and mechanical properties were examined; in particular, the biocompatibilities were evaluated in vivo and in vitro by the means of cell adhesion and cytotoxicity testing, short‐term subcutaneous implantation testing, and acute hemolysis testing according to the requirements of ISO 10993. The results showed the scaffold achieved the desirable levels of pliability (elastic up to 7.3% strain) and the appropriate breaking strength (2.22 MPa). The porosity of the SF‐gelatin layer was 87% and the pore diameter was 142 nm. After 12 days of cultivation, SEM observation demonstrated the scaffold was nontoxic, biocompatible, and capable of supporting 3T3 mouse fibroblasts attachment, spreading, and growth. The hemolysis test proved the scaffolds with hemolytic rates from 3.1 to 4.5%. The subcutaneous implantation test indicated minor inflammatory reactions surrounding the scaffolds and biodegradation were initially observed in about 3 months. The desired porous structure, strong and pliable properties, combined with the ability of PLA/SF‐gelatin scaffold to support cell growth in vitro, especially excellent biocompatibility in vivo, suggested potential application for tissue engineering scaffolds. © 2009 Wiley Periodicals, Inc. J Biomed Mater Res 2010
Collagen density significantly affects the functional properties of an engineered provisional scaffold
Authors: Abreu Eduardo L. , Palmer Matthew P. , Murray Martha M.
Published: June 2009

The formation of a provisional scaffold is essential in wound healing. However, for tissues inside of joints, this process is impeded by the synovial fluid environment and wound healing is significantly impaired as a result. Therefore, development of substitute provisional scaffolds which are effective in the intra‐articular environment is of great interest. Collagen‐platelet hydrogels have recently been found useful as substitute provisional scaffolding materials. In this study, our hypothesis was that increasing the collagen density in the hydrogel would result in physiologic changes that would be likely to affect their function as provisional scaffold substitutes. The primary functional outcome measures were modulus of the hydrogel, platelet activation, fibroblast proliferation, and scaffold retraction. Increased collagen density resulted in collagen‐platelet hydrogels with a higher storage modulus. Platelet activation was not found to be dependent on the collagen density within the range tested. Increasing the collagen density had a suppressive effect on both fibroblast proliferation and scaffold retraction. These studies suggest that the collagen density may be able to significantly influence the function of collagen‐platelet hydrogels used as substitute provisional scaffolds. © 2009 Wiley Periodicals, Inc. J Biomed Mater Res, 2010
Influence of interaction energy between Si‐doped diamond‐like carbon films and bacteria on bacterial adhesion under flow conditions
Authors: Shao Wei , Zhao Qi , Abel Eric W. , Bendavid Avi
Published: June 2009

Diamond‐like carbon (DLC) films, especially modified DLC films with doped elements as biomaterials for medical devices have been attracting great interest. In this article, the bacterial adhesion behavior on DLC films, Si‐doped DLC films, and stainless steel 316L was investigated with Pseudomonas aeruginosa ATCC 33347, which frequently causes medical device‐associated infections. This was done under laminar flow conditions in a flow chamber at 37°C. The contact angles of the coatings and the biofilm were measured. Polar liquids of distilled water and ethylene glycol, and apolar liquid of diiodomethane were used as a probe for surface free energy calculations. The electron donor component γ− of surface energy of Si‐doped DLC films increased with increasing the silicon content in the DLC films. The experimental results showed that the surface energy of the coatings and the interaction energy between the coatings and bacteria in water had significant influences on bacterial adhesion. The extended DLVO theory was used to explain the adhesion behavior. © 2009 Wiley Periodicals, Inc. J Biomed Mater Res, 2010
Intravital fluorescent microscopic evaluation of bacterial cellulose as scaffold for vascular grafts
Authors: Esguerra Maricris , Fink Helen , Laschke Matthias W. , Jeppsson Anders , Delbro Dick , Gatenholm Paul , Menger Michael D. , Risberg Bo
Published: June 2009

Although commonly used synthetic vascular grafts perform satisfactorily in large caliber blood vessels, they are prone to thrombosis in small diameter vessels. Therefore, small vessels might benefit from tissue engineered vascular grafts. This study evaluated bacterial cellulose (BC) as a potential biomaterial for biosynthetic blood vessels. We implanted the dorsal skinfold chambers in three groups of Syrian golden hamsters with BC (experimental group), polyglycolic acid, or expanded polytetrafluorethylene (control groups). Following implantation, we used intravital fluorescence microscopy, histology, and immunohistochemistry to analyze the biocompatibility, neovascularization, and incorporation of each material over a time period of 2 weeks. Biocompatibility was good in all groups, as indicated by the absence of leukocyte activation upon implantation. All groups displayed angiogenic response in the host tissue, but that response was highest in the polyglycolic acid group. Histology revealed vascularized granulation tissue surrounding all three biomaterials, with many proliferating cells and a lack of apoptotic cell death 2 weeks after implantation. In conclusion, BC offers good biocompatibility and material incorporation compared with commonly used materials in vascular surgery. Thus, BC represents a promising new biomaterial for tissue engineering of vascular grafts. © 2009 Wiley Periodicals, Inc. J Biomed Mater Res, 2010
The action of zymosan on octanoate transport and metabolism in the isolated perfused rat liver
Authors: Derbocio Alice M. , Lopez Carlos H. , Bracht Lívia , Bracht Adelar , Ishii‐Iwamoto Emy L.
Published: June 2009

The effects of zymosan on transport, distribution, and metabolism of octanoate in the perfused rat liver were investigated using the multiple‐indicator dilution technique. Livers were perfused with 300 µM octanoate in the absence or in the presence of 100 µg/mL zymosan. Tracer amounts of [1‐14C]octanoate, [3H] water, and [131I]albumin were injected into the portal vein, and the effluent perfusate was fractionated. The normalized dilution curves were analyzed by means of a space‐distributed variable transit time model. Zymosan decreased the space into which octanoate undergoes flow‐limited distribution, possibly the first cellular exchanging pool represented by plasma membranes and their adjacencies. However, the rate of transfer of octanoate from the plasma membrane into the rest of the cell was not modified as indicated by the similar values of the influx rates and also the net uptake of octanoate per unit of accessible cellular volume. However, when referred to the wet weight of the liver, the net uptake of octanoate was 37.5% reduced, a value corresponding to the diminution of the cellular accessible space. It can be concluded that an exclusion of a fraction of the liver parenchyma from the microcirculation is the main mechanism by which zymosan reduces the metabolism of exogenous octanoate. © 2009 Wiley Periodicals, Inc. J Biochem Mol Toxicol 23:155–165, 2009; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/jbt.20269
Studies on mode of action of hexaammine co(III) chloride against diethylnitrosamine‐induced hepatocarcinogenesis in mice
Authors: Naura Amarjit S. , Sharma Rajeshwar
Published: June 2009

We recently reported the anticarcinogenic potential of hexaammine cobalt(III) chloride, a synthetic complex of cobalt, on diethylnitrosamine (DENA)‐induced carcinogenesis. The present study was conducted to ascertain the possible mode of action of this compound on DENA‐induced hepatocarcinogenesis in male BALB/c mice. Time course evaluation of liver injury markers showed that the low dose of the compound is more effective in ameliorating DENA‐induced changes when administered for longer duration of time. Long‐term exposure of the compound significantly reversed the levels of diacylgylcerol (DAG) and nitric oxide synthase (NOS) induced by DENA, thus suggesting that the compound may hinder the process of chemical carcinogenesis potentially by downregulating the signal transduction mechanism involving DAG and NOS. Furthermore, short‐term intraperitoneal injection of the compound to mice 26 weeks after DENA initiation reduced the cell viability count in preneoplstic liver lesions in a dose‐dependent manner. In conclusion, our results showed that anticarcinogenic effects of hexaammine cobalt(III) chloride result from its influence on signal transduction events mediated through DAG together with its direct cytotoxic action against preneoplastic hepatic lesions induced by DENA in mice. © 2009 Wiley Periodicals, Inc. J Biochem Mol Toxicol 23:193–201, 2009; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/jbt.20280
Photopheresis therapy for problematic renal allograft rejection
Authors: Jardine Meg J. , Bhandari Sunil , Wyburn Kate R. , Misra Ashish K. , McKenzie Paul R. , Eris Josette M.
Published: June 2009

Background: Photopheresis is an immunomodulatory therapy for the treatment of T cell‐mediated disorders. It has been used for rejection prophylaxis in cardiac transplantation, adjuvant treatment of bronchiolitis obliterans in lung transplantation, treatment of graft verse host disease, and in a small number of cases, for treatment of acute rejection in renal transplantation. Little is known of long‐term outcomes following the use of photopheresis in solid organ transplantation. Methods: We report prospective follow‐up of our consecutive experience of the use of photopheresis as adjuvant/salvage therapy for problematic rejection in patients undergoing renal transplantation. Transplant graft survival, infective and malignant outcomes were reported. Results: A cohort of 10 renal transplants recipients received photopheresis therapy for therapy‐resistant rejection. Conventional therapy included an average of 6.2 g pulse methyl‐prednisolone and 17.1 days antilymphocyte therapy. The cohort received additional photopheresis therapy when the unresponsive nature of their rejections raised concerns of graft loss. Median follow‐up censored for patient loss was 66.7 months following photopheresis commencement. Rejection resolved in association with photopheresis use in all 10 patients. Six patients continued to have stable graft function (median serum creatinine: 191.5 μmol/L) at a median follow‐up of 71.0 months. There has been one patient death from sepsis and two from malignancy with functioning grafts while one graft has been lost to disease recurrence. Conclusion: Photopheresis may have a role as an adjuvant or salvage antirejection therapy in solid organ transplantation. Furthermore, evaluation in randomized controlled clinical trials is required to evaluate its potential. J. Clin. Apheresis, 2009. © 2009 Wiley‐Liss, Inc.
Expression of β‐1,4‐galactosyltransferase I in rat Schwann cells
Authors: Yang Huiguang , Yan Meijuan , Cheng Chun , Jiang Jing , Zhang Lili , Liu Jie , Zhou Zhengming , Shen Aiguo
Published: June 2009

Glycosylation is one of the most important post‐translational modifications. It is clear that the single step of β‐1,4‐galactosylation is performed by a family of β‐1,4‐galactosyltransferases (β‐1,4‐GalTs), and that each member of this family may play a distinct role in different tissues and cells. In the present study, real‐time PCR revealed that the β‐1,4‐GalT I mRNA reached peaks at 2 weeks after sciatic nerve crush and 3 days after sciatic nerve transection. Combined in situ hybridization for β‐1,4‐GalT I mRNA and immunohistochemistry for S100 showed that β‐1,4‐GalT I mRNAs were mainly located in Schwann cells after sciatic nerve injury. In conclusion, β‐1,4‐GalT I might play important roles in Schwann cells during the regeneration and degeneration of the injured sciatic nerve. In other pathology, such as inflammation, we found that LPS administration affected β‐1,4‐GalT I mRNA expression in sciatic nerve in a time‐ and dose‐dependent manner, and β‐1,4‐GalT I mRNA is expressed mainly in Schwann cells. These results indicated that β‐1,4‐GalT I plays an important role in the inflammation reaction induced by intraperitoneal injection of LPS. Similarly, we found that β‐1,4‐GalT I in Schwann cells in vitro was affected in a time‐ and concentration‐dependent manner in response to LPS stimulation. All these results suggest that β‐1,4‐GalT I play an important role in Schwann cells in vivo and vitro during pathology. In addition, β‐1,4‐GalT I production was drastically suppressed by U0126 (ERK inhibitor), SB203580 (p38 inhibitor), or SP600125 (SAPK/JNK inhibitor), which indicated that Schwann cells which regulated β‐1,4‐GalT I expression after LPS stimulation were via ERK, SAPK/JNK, and P38 MAP kinase signal pathways. J. Cell. Biochem. 108: 75–86, 2009. © 2009 Wiley‐Liss, Inc.
How Shriners Hospitals for Children found the formula for performance excellence
Authors: Noble Roger
Published: June 2009

Fragmented, people‐intensive processes and entrenched cultural issues are among the thorny realities of cost and quality improvement in healthcare settings. The unconventional hybrid approach of Shriners Hospitals for Children goes to the heart of the problem and also entailed a “middle‐out” deployment that tackled the politics of change. The author describes the strategy for building buy‐in and participation among clinicians and other staff and for demonstrating the program's potential benefits in order to eventually win board‐level endorsement. The program, which integrates a portfolio of improvement methodologies, project management training and tools, and change agents and change leaders from across the organization, is already producing measurable gains for the health system. © 2009 Wiley Periodicals, Inc.
IMI's Aspire program feeds its senior leader pipeline through self‐nominations
Authors: Stage Victoria , Houghton Russell
Published: June 2009

Self‐nominations, combined with sophisticated assessment and selection tools, have produced a more diverse pool of highly qualified talent that IMI, a worldwide engineering company, is now grooming for its top 40 senior leadership roles. A three‐step nomination and selection process for the enterprise‐level Aspire program includes 360‐degree‐type performance assessments; online testing of potential that measures foundational capabilities and predispositions as well as accelerators in order to assign a norm‐based percentile standing; and an assessment center with simulations for gauging readiness for senior leadership roles. Those selected as Aspire participants are afforded a range of activities, geared to individual and organizational needs, that include training/education, on‐the‐job and business‐driven development, and relationship‐driven development. © 2009 Wiley Periodicals, Inc.
Companies rehearse a very different future: Connecting leadership capability and strategy execution through simulation
Authors: Carucci Ron
Published: June 2009

How can an organization's leaders best learn the behaviors and competencies required in a very different future? “Rehearsing the future” simulations immerse leaders in a fictitious business context strategically similar to their company's desired future to solve critical issues as a leadership team. The author differentiates future rehearsal simulation from computer simulation; describes when, where, and why these simulations are effective; and details the process for building a simulation that integrates multiple leadership development tools. Two actual cases, a global technology corporation seeking a horizontally integrated platform of products and services and a biotech company determined to shorten its product development timelines, illustrate the benefits of simulation technology for leaders and the business. © 2009 Wiley Periodicals, Inc.
Conducting business in Greece: A brief for international managers
Authors: Nakos George E. , Hajidimitriou Yannis A.
Published: June 2009

Greece has emerged in recent years as an attractive business destination for international companies. European Union membership and the adoption of the euro have greatly changed the Greek economy. This article outlines recent changes in the Greek political and economic environment and the opportunities and challenges that international managers face in Greece. Energy, technology, tourism, and food and beverage industries are the hot sectors of the economy where foreign investors are expected to concentrate their interest in the future. © 2009 Wiley Periodicals, Inc.