bluuebunny/crossref_metadata_2025 huggingface dataset:
Overview of Approaches to the Identification of Inhibitors of Cytokine Action
Authors: Woska, Joseph R. , Magram Jeanne
Published: January 2005

Cytokines are key regulatory molecules that serve as critical mediators of cell‐to‐cell communication. They play a central role in immune function and are important molecular targets for drug discovery because of their dysregulation in immune disease. Initial attempts to develop agents that block the actions of cytokines focused on identifying small‐molecule antagonists that would directly compete with these cytokines for their cognate receptors. These efforts were, for the most part, unsuccessful. Outlined in this unit are strategies for developing new approaches. The first section describes strategies for how one might build a conceptual framework to approach this problem. The second section focuses on the technical approaches that can be utilized to accomplish the strategies outlined in the first section. These concepts are illustrated using interleukin‐2 (IL‐2) as a prototype, since there is a substantial body of knowledge regarding this cytokine, including information on its functions, signaling pathways, and physiological effects in normal and diseased tissue.
Animal Tests of Anxiety
Authors: File Sandra E. , Lippa Arnold S. , Beer Bernard , Lippa Morgen T.
Published: January 2005

Animal tests of anxiety are used to screen novel compounds for anxiolytic or anxiogenic activity, to investigate the neurobiology of anxiety, and to assess the impact of other occurrences such as exposure to predator odors or early rearing experiences. This unit presents protocols for the most commonly used animal tests of anxiety. The Geller‐Seifter conflict test, the social interaction test, light/dark exploration, the elevated plus‐maze, defensive burying, and the thirsty rat conflict. The protocols are described in terms of drug screening tests, but can be modified easily for other purposes.
Overview on the Use of Therapeutic Antibodies in Drug Discovery
Authors: Roguska Michael , Kaymakcalan Zehra , Salfeld Jochen
Published: January 2005

The number of therapeutic antibodies approved by regulatory agencies as novel drugs and the number of antibodies in development has increased significantly. The modular nature of antibody structure has enabled researchers to more predictably design therapeutic antibodies by choosing appropriate functional features most appropriate for a given antibody target and clinical indication. Advances in recombinant antibody technologies have allowed the routine generation of antibodies that can satisfy stringent drug design criteria, such as low immunogenicity, high affinity, target specificity, and commercially viable manufacturing methods. Engineering design opportunities exist for both the variable and the constant regions that encompass, in addition to antigen specificity and affinity, effector functions that mediate immune complex clearance or pharmacokinetics. These are discussed in the context of relevant in vivo and in vitro technologies, such as human IgG transgenic mice, phage display, and biologics manufacturing. Finally, therapeutic antibodies are compared with traditional drugs with respect to target class, selectivity, route of administration, intellectual property issues, and lead discovery and optimization.
Primary Observation (Irwin) Test in Rodents for Assessing Acute Toxicity of a Test Agent and its Effects on Behavior and Physiological Function
Authors: Roux Sylvain , Sablé Evelyne , Porsolt Roger D.
Published: January 2005

The Irwin observation test is commonly used to evaluate the effects of a new substance on behavior and physiological function. The results of the Irwin test are used to determine potential toxicity and to select doses for specific therapeutic activity. The Irwin test can also be used in a safety approach for detecting untoward effects of a new compound on general behavior and for evaluating its acute neurotoxicity. In particular, data obtained in the Irwin Test can help to determine the dose range to be tested in other safety tests. Furthermore, the Irwin Test can furnish a first but pertinent orientation towards a specific therapeutic indication, a specific mechanism of action or a specific physiological function.
Synthesis of Oligodeoxyribo‐ and Oligoribonucleotides According to the H‐Phosphonate Method
Authors: Strömberg Roger , Stawinski Jacek
Published: January 2005

Oligonucleotides can be synthesized by condensing a protected nucleoside H‐phosphonate monoester with a second nucleoside in the presence of a coupling agent to produce a dinucleoside H‐phosphonate diester. This can then be converted to a dinucleoside phosphate or to a backbone‐modified analog such as a phosphorothioate or phosphoramidite. This unit discusses four alternative methods for synthesizing nucleoside H‐phosphonate monoesters. The methods are efficient and experimentally simple, and use readily available reagents. The unit describes the activation of the monoesters, as well as competing acylation and other potential side reactions.
Evaluating Neutralizing Antibodies Against HIV, SIV, and SHIV in Luciferase Reporter Gene Assays
Authors: Montefiori David C.
Published: January 2005

Neutralizing antibody assays are powerful tools for assessing humoral immunity in AIDS virus infection and vaccine development. Although many different assays have been described, all are based on the same principle, measuring reductions in virus infectivity. This unit describes two assays utilizing a genetically engineered cell lines that are susceptible to infection by most strains of HIV‐1, SIV, and SHIV. One assay is designed for optimal performance with uncloned viruses produced in either PBMC or CD4+ T cell lines. A second assay is designed for single‐cycle infection with molecularly cloned pseudoviruses produced by transfection in 293T cells. Both assays are performed in a 96‐well format and use tat‐responsive luciferase reporter gene expression as readout.
In Situ Staining Using MHC Class I Tetramers
Authors: Skinner Pamela J. , Haase Ashley T.
Published: January 2005

The invention of MHC‐tetramer technology to label antigen‐specific T cells has lead to a greatly enhanced understanding of T lymphocyte biology. This protocol describes the use of MHC class I tetramers to stain antigen‐specific T cells in tissue sections. In situ tetramer staining (IST) can be used to determine the localization, abundance, and phenotype of antigen‐specific T cells in native environments and in three‐dimensional space. IST is broadly applicable because it can be used to stain essentially any antigen‐specific T cell in any tissue for which MHC tetramers are available. IST can be combined with histochemistry and/or immunohistochemistry to permit visualization and characterization of antigen‐specific T cells relative to other cell types in stained tissue sections. Thus, IST is a useful and valuable component of MHC‐tetramer technology.
Fluorescence Lifetime Imaging Microscopy
Authors: Esposito Alessandro , Wouters Fred S.
Published: January 2005

Fluorescent lifetime imaging microscopy is a powerful tool to enhance the contrast in images of biological samples and to investigate the local environment of a fluorochrome. FLIM allows the detection of protein‐protein interactions and their biochemical state by the quantitative detection of Förster resonance energy transfer (FRET) between molecules in living cells or tissues. The availability of different spectral variants of the visible fluorescent proteins (VFPs) allows the investigation of molecular activities and protein‐protein interactions in living cells by FRET as measured by FLIM.
Analysis of Fibronectin Matrix Assembly
Authors: Wierzbicka‐Patynowski Iwona , Mao Yong , Schwarzbauer Jean E.
Published: January 2005

The extracellular matrix acts as a framework for tissue architecture and dynamically regulates many cellular functions. Fibronectin is a ubiquitous extracellular matrix component that plays critical roles in matrix structure and in directing cell behaviors. Fibronectin is synthesized and secreted by many cell types including fibroblasts, endothelial cells, myoblasts, and astrocytes. Upon secretion, cells assemble fibronectin into a fibrillar network. During assembly, fibronectin is initially organized into fine cell‐associated fibrils and, through continued accumulation of fibronectin, these fibrils are converted into a dense network of detergent‐insoluble fibrils. Differential solubility in the detergent deoxycholate is the principle for biochemical fractionation of fibronectin matrix. Fibril assembly and organization can also be examined by immunofluorescence staining. In this unit, basic methods of detection, quantification, and visualization of fibrillar fibronectin matrix are described.
Comparative Genomic Hybridization
Authors: Bayani Jane , Squire Jeremy A.
Published: January 2005

Comparative genomic hybridization (CGH) is a screening method based on fluorescence in situ hybridization (FISH). In contrast to conventional FISH, the metaphase target is derived from a normal peripheral blood lymphocyte culture. This target is hybridized to the test or tumor DNA, which is labeled/detected by one fluorochrome (i.e., green), and to an equal amount of labeled normal or reference DNA, which is labeled/detected by a different fluorochrome (red). It is the difference in these green/red ratios (determined by specialized software) along the length of each karyotyped chromosome that indicates the relative copy number changes in the test/tumor DNA. The basic FISH techniques reviewed in this section, the parameters for which also apply to obtaining satisfactory results for CGH, include cytogenetic preparation and slide‐making, DNA extraction (from fresh or paraffin‐embedded tissues) and labeling, slide pretreatment, hybridization, post‐hybridization washes, and detection.
Sister Chromatid Exchange
Authors: Bayani Jane , Squire Jeremy A.
Published: January 2005

Sister chromatid exchange (SCE) refers to the interchange of DNA between replication products. The technique for detecting such exchanges takes advantage of the semiconservative nature of DNA synthesis. 5′‐bromodeoxyuridine (BrdU) is incorporated into the newly synthesized DNA. Using standard culturing techniques, Colcemid is added to the culture and conventional cytogenetic preparations are made. Differential staining with Hoechst dye and Giemsa allows the newly synthesized DNA within a chromatid to be recognized, since BrdU incorporation results in much weaker staining. SCEs represent a point of DNA template exchange during strand synthesis, visualized as asymmetric chromatid staining or “harlequin” chromosomes.
Microarray Data Visualization and Analysis with the Longhorn Array Database (LAD)
Authors: Killion Patrick J. , Iyer Vishwanath R.
Published: January 2005

The wide availability and use of DNA microarrays has brought the power of whole‐genome functional characterization to a large variety of research environments. Microarrays, however, also introduce significant infrastructural and analytical concerns with respect to the long‐term warehousing, annotation, and visualization of immense data sets. The Longhorn Array Database (LAD) is a MIAME‐compliant microarray database that operates on PostgreSQL and Linux. It is a free and completely open‐source software solution, and provides a systematic and proven environment in which vast experiment sets can be safely archived, securely accessed, biologically annotated, quantitatively analyzed, and visually explored. This unit provides the complete set of information needed to successfully deploy, configure, and use LAD for the purposes of two‐color DNA microarray analysis and visualization.
Model reference adaptive control using a low‐order controller
Authors: Miller Daniel E.
Published: January 2005

In the model reference adaptive control problem, the goal is to force the error between the plant output and the reference model output asymptotically to zero. The classical assumptions on a single‐input–single‐output (SISO) plant is that it is minimum phase, and that the plant relative degree, the sign of the high‐frequency gain, and an upper bound on the plant order are known. Here we consider a modified problem in which the objective is weakened slightly to that of requiring that the asymptotic value of the error be less than a (arbitrarily small) pre‐specified constant. Using recent results on the design of generalized holds for model reference tracking, here we present a new switching adaptive controller of dimension two which achieves this new objective for every minimum phase SISO system; no structural information is required. Copyright © 2001 John Wiley & Sons, Ltd.
Designing predictors for MIMO switching supervisory control
Authors: Mosca Edoardo , Capecchi Francesco , Casavola Alessandro
Published: January 2005

The paper studies the problem of inferring the behaviour of a linear feedback loop made up by an uncertain MIMO plant and a given candidate controller from data taken from the plant possibly driven by a different controller. In such a context, it is shown here that a convenient tool to work with is a quantity called normalized discrepancy. This is a measure of mismatch between the loop made up by the unknown plant in feedback with the candidate controller and the nominal ‘tuned‐loop’ related to the same candidate controller. It is shown that discrepancy can in principle be obtained by resorting to the concept of a virtual reference, and conveniently computed in real time by suitably filtering an output prediction error. The latter result is of relevant practical value for on‐line implementation and of paramount importance in switching supervisory control of uncertain plants, particularly in the case of a coarse distribution of candidate models. Copyright © 2001 John Wiley & Sons, Ltd.
Stochastic adaptive control using multiple models for improved performance in the presence of random disturbances
Authors: Narendra Kumpati S. , Driollet Osvaldo A.
Published: January 2005

The use of multiple models for adaptively controlling an unknown continuous‐time linear system was proposed in Narendra and Balakrishnan (IEEE Transactions on Automatic Control 1994; 39(9):1861–1866). and discussed in detail in Narendra and Xiang (IEEE Transactions on Automatic Control 2000, 45(9):(1669–1686) Technical Reports 9801 and 9803, Centre for System Science, Yale University, 1998). Recently, the same concepts were extended to discrete‐time systems, both for the noise free case as well as when a stochastic disturbance is present, and the convergence of the algorithms was established. In this paper we consider structurally different estimation models, and use the multiple models approach to select, on‐line, the one that results in the best performance of the overall system for the given disturbance characteristics. The principal objective of the paper is to demonstrate that the convergence of these schemes can be treated in a unified manner. Simulations are included towards the end of the paper to indicate the improvement in performance that can be achieved using such schemes. Copyright © 2001 John Wiley & Sons, Ltd.
Boundary control of a two‐dimensional flexible rotor
Authors: Nagarkatti S. P. , Dawson D. M. , de Queiroz M. S. , Zhang F. , Costic B.
Published: January 2005

In this paper, we present the design of boundary controllers for a two‐dimensional, spinning flexible rotor system. Specifically, we develop a model‐based boundary controller which exponentially regulates the rotor's displacement and the angular velocity tracking error, and an adaptive boundary controller which asymptotically achieves the same control objective while compensating for parametric uncertainty. As opposed to previous boundary control work, which focused on the velocity setpoint problem and placed restrictions on the magnitude of the desired angular velocity setpoint, the proposed control architecture achieves angular velocity tracking with no restrictions on the magnitude of the desired velocity trajectory. Experimental results conducted on a flexible rotor tested are presented to illustrate the feasibility of implementing the proposed boundary control laws. Copyright © 2001 John Wiley & Sons, Ltd.
Simple Detachment Patterning of Organic Layers and Its Application to Organic Light‐Emitting Diodes
Authors: Choi J. , Kim D. , Yoo P. J. , Lee H. H.
Published: January 2005

A new detachment patterning technique is applied to the fabrication of a green organic light‐emitting diode (OLED). The method (applicable to organic and inorganic substrates) involves simply placing a patterned PDMS mold in conformal contact with the organic layer to be patterned, annealing at a temperature below the glass transition temperature for a period of time, and then removing the mold after cooling to room temperature. The parts of the organic layer in contact with the mold become detached from the substrate upon removing the mold.
A Novel Method for Fixing the Anisotropic Orientation of Dispersed Organic Nanocrystals in a Magnetic Field
Authors: Kaneko Y. , Shimada S. , Fukuda T. , Kimura T. , Yokoi H. , Matsuda H. , Onodera T. , Kasai H. , Okada S. , Oikawa H. , Nakanishi H.
Published: January 2005

Fixing of the anisotropic orientation of DAST nanocrystals, trans‐4‐[4‐(dimethylamino)]stilbazolium p‐toluenesulfonate, a well‐known organic second‐order nonlinear optical material, is described. The DAST nanocrystals were oriented in an acrylate monomer by an applied magnetic field and then immobilized by UV‐curing. The optical anisotropy of the absorption and refractive index of the obtained solid—which is odorless, transparent, heat resistant, insoluble, and soft, like rubber—is shown to be easily controlled by the magnetic field. See also front cover.
Cover Picture: A Novel Method for Fixing the Anisotropic Orientation of Dispersed Organic Nanocrystals in a Magnetic Field (Adv. Mater. 2/2005)
Authors: Kaneko Y. , Shimada S. , Fukuda T. , Kimura T. , Yokoi H. , Matsuda H. , Onodera T. , Kasai H. , Okada S. , Oikawa H. , Nakanishi H.
Published: January 2005

The cover illustrates trans‐4‐[4‐(dimethylamino)]stilbazolium p‐toluenesulfonate (DAST) nanocrystals as white rectangular parallelepipeds anisotropically oriented by an applied magnetic field. As reported by Kaneko and co‐workers on p. 160, the oriented DAST nanocrystals dispersed in lauryl acrylate monomer can be easily fixed by UV curing in a magnetic field. The inset displays a picture of the cured DAST dispersions with a quarter for scale.
Preparation of Tb(Pht)3Phen/rubber composites and characterization of their fluorescent properties
Authors: Yang Cheng , Liu Li , Lu Yonglai , He Lei , Zhang Wan , Zhang Liqun
Published: January 2005

A rare‐earth ternary complex compound, Tris‐(terbium‐phthalate)‐1, 10‐phenanthroline Terbium (III) [Tb(Pht)3Phen], was synthesized through the reaction among a rare‐earth oxide (Tb4O7), potassium hydrogen phthalate and phenanthroline, and its structure was characterized with scanning electron microscopy (SEM), laser particle size (LPS), IR, and X‐ray diffraction. This was the first time that Tb(Pht)3Phen/rubber [nitrile butadiene rubber (NBR) or methyl vinyl silicone rubber (SiR)] composites had been prepared through mechanical mixing processing. SEM revealed that the dimensions of Tb(Pht)3Phen dispersed in matrix rubber were much smaller than those of the original particles of the complex compound. The Tb(Pht)3Phen/rubber composites showed much better luminescent performance than the Tb(Pht)3Phen complex compound. The fluorescent intensities of the Tb(Pht)3Phen/rubber composites were strongly dependant on the concentration of Tb(Pht)3Phen, and 30 phr was the optimal concentration for both the Tb(Pht)3Phen/NBR and Tb(Pht)3Phen/SiR composites. Within the concentration range of Tb(Pht)3Phen used in this work, the fluorescent intensions of the SiR composites were stronger than those of their NBR counterparts. © 2005 Wiley Periodicals, Inc. J Appl Polym Sci 96: 20–28, 2005
Some physical properties of various amine‐pretreated Nomex Aramid yarns
Authors: Wang Chyung‐Chyung , Chen Cheng‐Chi
Published: January 2005

In this study we pretreated Aramid yarns with ethylenediamine (EDA), diethylene triamine (DETA), and triethylene tetraamine (TETA) under different conditions to study some of their physical properties. The tensile strength retention, dye absorption (basic dye), and wicking height changed increasing pretreatment temperature, time period, and amines concentration. The glass‐transition temperature and the density of the crystals were ranked as follows: EDA > DETA > TETA; however, the degrees of the surface void were inverse. We concluded that the polymer chains of the Aramid fibers were rearranged through shrinkage of the pretreated Aramid fibers during pretreatment, and the hydrolysis of the Nomex polymer chains occurred under higher amine concentrations. The former phenomena were confirmed with differential scanning calorimetry, dynamic mechanical analysis, and X‐ray diffraction analyses, and the latter were confirmed with Fourier transform infrared spectroscopy and basic dye adsorption analysis. © 2005 Wiley Periodicals, Inc. J Appl Polym Sci 96: 70–76, 2005
Finding support for educational projects in anatomy: Tips, tools, and lessons learned
Authors: Granger Noelle A. , Calleson Diane
Published: January 2005

This article is based on a presentation of the same name given on 20 April 2004 at a symposium entitled “Faculty Development: Funding Resources for Education Projects” at the annual meeting of the American Association of Anatomists in Washington, DC. It discusses various lessons learned by the authors from their own work on the development of an educational tool and the assessment of its use with funding from an educational research grant, as well as tips and tools gathered from other education researchers. The material is organized into two sections. The first provides information and suggestions useful in the development of an educational project in anatomy and the preparation of the grant application. The second consists of insights that may help ensure that the funded grant is successful. Anat Rec (Part B: New Anat) 282B:13–17, 2005. © 2005 Wiley‐Liss, Inc.
Bailing and jailing the fast and frugal way
Authors: Dhami Mandeep K. , Ayton Peter
Published: January 2005

Legal decisions such as the decision to bail upon adjourning a case have major consequences for both defendants and society. In the English system, magistrates, most of whom are lay people, are afforded considerable discretion and must work under constraints such as time pressure. Judgment analysis of the bail decision making policies of 81 magistrates from 44 courts throughout England and Wales revealed intra‐ and inter‐magistrate inconsistency in bail decisions, discrepancies between stated and elicited cue use, and high levels of post‐decisional confidence. Furthermore, magistrates' policies were better described and predicted by a fast and frugal model characterized by noncompensatory cue use, than by either of two compensatory integration models. The fast and frugal model portrays a picture of bail decision making that conflicts with the ideal practice as defined by the due process model of justice. We discuss the implications of these findings for judgment and decision making research and criminal justice policy. Copyright © 2001 John Wiley & Sons, Ltd.
Increased carbon disulfide‐stimulated chemiluminescence in the pyrogallol–luminol system
Authors: Jian Le
Published: January 2005

We studied the effect of carbon disulphide (CS2) on the generation of superoxide anion $(\hbox{O}_{2}^{-\cdot})$ and its chemiluminescence (CL) in the pyrogallol–luminol system. Testing was conducted with the pyrogallol–luminol system to observe the CL dynamic curve of CS2 and the inhibition by superoxide dismutase (SOD) on CL induced by CS2. Compared with the ethanol solvent control, CS2 enhanced the emission intensity of CL and delayed the peak time. There was a significant dose–concentration relationship between CS2 concentrations (10, 40, 80 mg/mL) and CL peak (r = 0.975 p = 0.012) and CS2 concentrations and peak time (r = 0.990, p = 0.005). The CL peak at 80 mg/mL CS2 was higher than that in a background without ethanol. The enhanced CL evoked by CS2 could be inhibited by SOD. The results suggest that CS2 can induce the pyrogallol–luminol system to generate an increased amount of $\hbox{O}_{2}^{-\cdot}$ and delay the CL peak time. Copyright © 2001 John Wiley & Sons, Ltd.
Changes in phagocyte activity in patients with ischaemic stroke
Authors: Alexandrova Margarita L. , Bochev Petyo G. , Markova Vanya I. , Bechev Blagovest G. , Popova Marina A. , Danovska Maya P. , Simeonova Virginia K.
Published: January 2005

The activity of peripheral phagocytes to generate reactive oxygen species (ROS) was studied in healthy individuals and patients with ischaemic stroke. The aim was to clarify the relationship between phagocyte activity, the time elapsed after the onset of disease and stroke severity. The total and extracellular production of ROS were evaluated by luminol chemiluminescence. Simultaneously the plasma oxidant activity was determined. When stimulated by opsonized zymosan, phagocytes in patients with stroke (regardless of its severity) showed fast activation. The total ROS generation increased over time in all stroke cases studied. However, the extracellular ROS generation was found to be greater in patients with severe stroke than in those with mild neurological deficiency. When stimulated by formyl‐methionyl‐leucyl‐phenylalanine, the total oxidative phagocyte capacity (regardless of stroke severity) increased over time, but there was no change in the amount of extracellularly generated ROS. In patients with stroke the oxidant activity of plasma was enhanced. We conclude that circulating phagocytes in patients with ischaemic stroke are primed for enhanced ROS production by opsonin receptor‐mediated stimulation and for increased secretion of myeloperoxidase by opsonin receptor‐independent stimulation. The enhanced extracellular generation of ROS through opsonin receptor‐dependent stimulation may be considered an oxidative stress biomarker in cerebral ischaemia. Copyright © 2001 John Wiley & Sons, Ltd.
Development, parallelization, and automation of a gas‐inducing milliliter‐scale bioreactor for high‐throughput bioprocess design (HTBD)
Authors: Puskeiler R. , Kaufmann K. , Weuster‐Botz D.
Published: January 2005

A novel milliliter‐scale bioreactor equipped with a gas‐inducing impeller was developed with oxygen transfer coefficients as high as in laboratory and industrial stirred‐tank bioreactors. The bioreactor reaches oxygen transfer coefficients of >0.4 s−1. Oxygen transfer coefficients of >0.2 s−1 can be maintained over a range of 8‐ to 12‐mL reaction volume. A reaction block with integrated heat exchangers was developed for 48‐mL‐scale bioreactors. The block can be closed with a single gas cover spreading sterile process gas from a central inlet into the headspace of all bioreactors. The gas cover simultaneously acts as a sterile barrier, making the reaction block a stand‐alone device that represents an alternative to 48 parallel‐operated shake flasks on a much smaller footprint. Process control software was developed to control a liquid‐handling system for automated sampling, titration of pH, substrate feeding, and a microtiter plate reader for automated atline pH and atline optical density analytics. The liquid‐handling parameters for titration agent, feeding solution, and cell samples were optimized to increase data quality. A simple proportional pH‐control algorithm and intermittent titration of pH enabled Escherichia coli growth to a dry cell weight of 20.5 g L−1 in fed‐batch cultivation with air aeration. Growth of E. coli at the milliliter scale (10 mL) was shown to be equivalent to laboratory scale (3 L) with regard to growth rate, μ, and biomass yield, YXS. © 2005 Wiley Periodicals, Inc.
TGF‐β1 regulation in hepatocyte‐NIH3T3 co‐culture is important for the enhanced hepatocyte function in 3D microenvironment
Authors: Chia Ser‐Mien , Lin Pao‐Chun , Yu Hanry
Published: January 2005

Co‐culture of hepatocytes or hepatocyte spheroids with the supporting NIH3T3 in a 3D microcapsule formed with a hybrid natural/synthetic matrix has led to enhanced hepatocyte functions. We investigated the mechanism of the functional enhancement in co‐culture with respect to the contributions of soluble factors and direct cell–cell interactions. The conditioned media from the co‐culture induced higher P450 cytochrome oxidase activity (indicated by EROD assay) in the microencapsulated hepatocytes than the conditioned media from the NIH3T3‐ or the hepatocytes‐alone controls. Conditioned media from physically separated co‐culture of hepatocytes‐NIH3T3 by a membrane insert reduced the functional enhancement. Among the known stimulators of hepatocyte functions, TGFβ1 is primarily responsible for the stimulation of hepatocyte functions in this 3D co‐culture since the removal of TGFβ1 by antibody depletion eliminated the functional enhancement and the reconstitution of TGFβ1 restored the functional enhancement. Activation of latent TGFβ1 in an extracellular environment were upregulated in co‐culture with no observable increase in the TGFβ1 expression at transcriptional and translational levels. Our data led to an improved understanding of how co‐culture enhances hepatocyte functions in vitro and pave the way for further innovations in liver tissue engineering, drug metabolism studies, and other applications that require functional hepatocytes cultured in vitro. © 2005 Wiley Periodicals, Inc.
Interleukin 7 upregulates vascular endothelial growth factor D in breast cancer cells and induces lymphangiogenesis in vivo
Authors: Al-Rawi M A A , Watkins G , Mansel R E , Jiang W G
Published: January 2005

Background

Interleukin (IL) 7 is known to stimulate growth of breast cancer cells in vitro. It has been recently associated with node-positive tumours and with poor survival in breast cancer. The effects of IL-7 on the lymphangiogenic properties of breast cancer cells were explored.

Methods

The effects of IL-7 on the expression of vascular endothelial growth factors (VEGFs) in MDA MB-231, MCF-7 and BT-483 cells were analysed by reverse transcriptase–polymerase chain reaction and western blotting. An in vivo lymphangiogenesis model using nude mice was developed. The newly generated microtubules were stained with anti-von Willebrand factor and anti-LYVE-1 (lymphatic vessel endothelial hyaluronan receptor) antibodies.

Results

All VEGFs (VEGF-A, -B, -C and -D) were expressed in breast cancer cells, but at different levels. IL-7 increased the expression of VEGF-D at both mRNA and protein levels in MCF-7 and MDA MB-231 cells. In the in vivo model, IL-7 significantly induced the formation of lymphatic LYVE-1-positive, but not vascular von Willebrand factor-positive, microtubules (P = 0·021 versus sections without IL-7).

Conclusion

IL-7 induced the lymphangiogenic properties of breast cancer cells, probably by upregulation of VEGF-D. This might have a significant impact on the lymphatic spread of breast cancer.
Axillary vein abnormalities contribute to development of lymphoedema after surgery for breast cancer
Authors: Pain S J , Vowler S , Purushotham A D
Published: January 2005

Background

The aetiology of breast cancer-related lymphoedema (BCRL) is poorly understood and multifactorial. Previous work has suggested that acquired abnormalities of the axillary vein may contribute to arm swelling. This prospective study evaluated venous changes in patients with a new diagnosis of breast cancer who had surgery that included axillary lymph node clearance.

Methods

Patients underwent arm volume measurement and Doppler ultrasonographic assessment of the axillary vein before, and at 3 and 12 months after surgery.

Results

A complete data set was available for 70 patients. BCRL was observed in 16 per cent at 3 months and 11 per cent at 12 months. Significant alterations to venous flow patterns were observed in those with BCRL. Vein wall movement was significantly reduced after surgery for the group as a whole, but did not correlate with arm swelling. Venous stenosis with impaired flow was also observed in the absence of BCRL.

Conclusion

Axillary clearance can cause altered flow within the axillary vein, which is associated with an increased risk of developing lymphoedema.
Prospective evaluation of the impact of [18F]fluoro-2-deoxy-d-glucose positron emission tomography of resectable colorectal liver metastases
Authors: Truant S , Huglo D , Hebbar M , Ernst O , Steinling M , Pruvot F-R
Published: January 2005

Background

The aim of this study was to assess the additional value of information provided by positron emission tomography (PET) with [18F]fluoro-2-deoxy-d-glucose (FDG) over that provided by computed tomography (CT) in patients with resectable liver metastases from colorectal cancer.

Methods

Between October 2001 and November 2002, a prospective double-blind comparison of preoperative FDG-PET and thoracoabdominal CT was performed in 53 patients with potentially resectable liver metastases from colorectal cancer. All resected metastases were subjected to histological examination.

Results

Histological examination confirmed the presence of malignant or benign lesions detected by PET and/or CT in 95 per cent of instances. Overall sensitivity (78 per cent) and accuracy (88 per cent) of PET were equivalent to those of CT (76 and 86 per cent respectively). The sensitivity of PET was equivalent to that of CT for hepatic sites (both 79 per cent), but was superior for extrahepatic abdominal sites (63 and 25 per cent respectively). PET provided additional information in five patients, mainly by revealing abdominal extrahepatic metastases, but falsely upstaged three patients.

Conclusion

Whole-body FDG-PET may identify unrecognized extrahepatic metastases in patients with potentially resectable liver metastases imaged by CT. However, additional information provided by PET is not as reliable as suggested by earlier retrospective studies.
Socioeconomic deprivation has an adverse effect on outcome after ileostomy closure
Authors: Moug S J , Robertson E , Angerson W J , Horgan P G
Published: January 2005

Strong association between deprivation and outcome
Lymph node involvement in macroscopic medullary thyroid carcinoma
Authors: Tamagnini P , Iacobone M , Sebag F , Marcy M , De Micco C , Henry J F
Published: January 2005

Background

Medullary thyroid carcinoma (MTC) is a rare disease, with variable tendency to lymphatic spread. The aim of this retrospective study was to identify distinctive features of large MTC with and without nodal metastases.

Methods

Between 1993 and 2003, 28 consecutive patients underwent total thyroidectomy and neck node dissection for sporadic MTC larger than 10 mm in diameter.

Results

All tumours were confirmed to be malignant with a locally invasive pattern of growth. Lymph node metastases were present in 16 patients (N1) and absent in 12 (N0). There were no statistically significant differences between patients with N0 and N1 tumours concerning age (mean 52·1 versus 53·4 years), male:female ratio (0·7 versus 1·0), basal preoperative calcitonin concentration (mean 3238 versus 3076 pg/ml) and tumour size (23·3 versus 23·9 mm). There were differences in the incidence of tumour invasion (P < 0·001), vascular embolism (P = 0·011) and peritumoral thyroiditis (P = 0·039). Measurement of basal and stimulated calcitonin levels after surgery confirmed biochemical cure in all patients with N0 tumours and half of those with N1 disease (P = 0·006).

Conclusion

There were no preoperative factors that predicted node status for MTC larger than 1 cm in this series. Total thyroidectomy and nodal dissection remains the optimal treatment.
Effect of preoperative biliary stenting on immediate outcome after pancreaticoduodenectomy
Authors: Jagannath P , Dhir V , Shrikhande S , Shah R C , Mullerpatan P , Mohandas K M
Published: January 2005

Background

Preoperative biliary stenting is associated with bacterial contamination of bile and an increased rate of infectious complications after pancreaticoduodenectomy. Preoperative drainage has been found to have conflicting effects on morbidity and mortality, and no studies have been published on the effect of stent complications and duration of stenting on postoperative outcome. This study examined the effects of preoperative biliary stenting on early outcome after pancreaticoduodenectomy.

Methods

Details of 144 patients undergoing pancreaticoduodenectomy from 1992 to 2001 were entered into a database. Variables included biliary stenting, duration of stenting, stent complications and bile culture results. Details of surgery and postoperative complications were noted. Patients were grouped as stented and non-stented. Factors likely to affect postoperative mortality and morbidity were analysed.

Results

Preoperative biliary stenting was performed in 74 of the 144 patients; post-stenting complications developed in 18 patients (24 per cent) before surgery. After surgery there were nine deaths (6·3 per cent) and 60 (41·7 per cent) of the 144 patients developed complications, with no significant difference in morbidity rate between stented and non-stented patients. Logistic regression showed that a positive intraoperative bile culture was the only factor significantly associated with operative morbidity (P < 0·001) and mortality (P = 0·019). Biliary stenting was not significantly associated with a positive culture (P = 0·073), but stenting that resulted in complications (P = 0·006) and drainage for less than 6 weeks (P = 0·011) was associated with significantly greater culture positivity. Stenting followed by complications was shown by logistic regression to be the only factor significantly associated with a positive culture (P = 0·012).

Conclusion

A positive intraoperative bile culture was associated with higher morbidity and mortality rates following pancreaticoduodenectomy. A positive culture in the stented group was related to stent complications and duration of stenting. Uncomplicated stenting was not associated with increased morbidity or mortality.
Clinical relevance of multiple sentinel nodes in patients with breast cancer
Authors: Goyal A , Newcombe R G , Mansel R E
Published: January 2005

Background

Indiscriminate removal of axillary nodes may not be justified as it may potentially worsen the morbidity of the sentinel lymph node biopsy (SNB) procedure. This study examined the factors associated with removal of multiple sentinel lymph nodes and determined whether there was an upper threshold for the number of sentinel nodes that should be removed.

Methods

A total of 803 patients with breast cancer underwent successful SNB using peritumoral injection of 99mTc-labelled albumin colloid and Patent Blue V dye. SNB was followed by standard axillary treatment at the same operation in all patients.

Results

The mean number of sentinel nodes removed per procedure was 2·2 (range 1–9). Multiple sentinel nodes (mean 2·9, range 2–9) were found in 501 patients (62·4 per cent). The false-negative rate in patients who had one sentinel node harvested was 10 per cent, compared with 1 per cent in patients who had three or more nodes removed (P = 0·010). Factors associated with finding multiple sentinel nodes were age less than 50 years (P = 0·004), low body mass index (P < 0·001), tumour in the outer half of the breast (P = 0·013), sentinel node visualization on lymphoscintigraphy (P < 0·001) and an interval of 12 h or less between radioisotope injection and SNB (P = 0·014). For 99·6 per cent of node-positive tumours, metastasis was detected within the first four sentinel nodes removed.

Conclusion

The identification of multiple sentinel nodes, when present, reduced the false-negative rate. These data suggested that removal of more than four nodes was unnecessary.
Addiction as a functional representation
Authors: Heim Derek , Davies John B. , Cheyne Bill , Smallwood Jonathan
Published: January 2005

This study examined how perceptions of the addicted state vary as a function of social conditions, personal circumstances and type of substance. University students (n = 144) were presented with portrayals of drug users in which sex, drug type and social setting were varied. A questionnaire determined the degree to which participants thought that the person portrayed was (i) addicted, (ii) prone to use drugs due to his/her personality, and (iii) perceived as a problem to society. The pattern of results fitted a functional model of the addiction concept rather than an attempt to describe an ‘objective’ state. Copyright © 2001 John Wiley & Sons, Ltd.
Attitudes to women in society: the role of social dominance orientation and social values
Authors: Bates Cathy , Heaven Patrick C. L.
Published: January 2005

his research assessed the extent to which attitudes to women in society are predicted by the personality trait social dominance orientation (SDO) as well as the values international harmony and equality (INT) and national strength and order (NAT). Respondents were a community sample of adult non‐students (N = 158). Sex differences were observed on INT and attitudes to women. Multiple regression analyses showed sex differences in the extent to which SDO predicts attitudes to women, while no support was found for the view that social attitudes are underpinned by both security and harmony values. The results are discussed with reference to social dominance theory and the nature of the security value domain. Copyright © 2001 John Wiley & Sons, Ltd.
Community‐oriented primary care: a multidisciplinary community‐oriented approach to primary care?
Authors: Lenihan Penny , Iliffe Steve
Published: January 2005

Developing more of a local public health focus, and involving local communities in Great Britain in health care decision‐making, are key aspects of the radically changing face of primary care. Community‐oriented primary care (COPC) is an international model for innovative primary health care delivery historically applied in developing or deprived communities, but increasingly seen as having broader relevance for a wider range of primary care settings. COPC has a long history of development in deprived communities, it is still however seen as innovative. It fits the current requirements of clinical governance and the ‘Modern and Dependable NHS’, but does its long history also provide information about it's pitfalls? COPC is promoted as an approach that is applicable to community mental health problems, community psychologists can provide the expertise to facilitate addressing community mental health in COPC programmes. This paper describes the COPC model and highlights the relevance of the COPC philosophy and the problems of its implementation for community psychologists in primary care. Copyright © 2001 John Wiley & Sons, Ltd.
Mental health professionals' support of self‐help groups
Authors: Salzer Mark S. , Rappaport Julian , Segre Lisa
Published: January 2005

Objective. Self‐help groups and other consumer‐led services are viewed as valuable additions to mental health services. This study describes professional support for self‐help groups and examines the hypothesis that professional support of self‐help is influenced by the degree to which professionally‐led groups are viewed as more helpful than self‐help groups. Method. Survey data were obtained from a representative sample of over 900 mental health professionals employed in mental health agencies in a large US State. The survey assessed beliefs, behaviours, attitudes, and intentions toward professional and self‐help groups. Results. Respondents who perceive professionally‐led groups to be significantly more helpful than self‐help groups were less inclined to support self‐help groups through referrals, help in organizing groups, or financially. Conclusion. To the extent that professional support of the self‐help movement is diminished, valuable allies in the struggle to expand the reach of mental health services are lost. It is proposed that mental health professionals should obtain additional information about the benefits of self‐help and the constructive role that self‐help groups can play in expanding the availability and continuum of beneficial mental health services. Copyright © 2001 John Wiley & Sons, Ltd.
Pragmatic post‐structuralism (I): participant observation and discourse in evaluating violence intervention
Authors: O'Neill Damian , Morgan Mandy
Published: January 2005

This paper discusses the process and merits of a post‐structuralist approach to participant observation and describes the use of this research strategy in evaluating a community based ‘stopping violence’ programme. While the participant observation research strategy is commonly employed as a ‘process evaluation’ method (Rossi and Freeman, 1993) it's role within a distinctly post‐structuralist programme is a novel application of a well‐established research strategy. This has significant implications for how social scientists may approach both participant observation and evaluation in the future. Copyright © 2001 John Wiley & Sons, Ltd.
Stereotype change and prejudice reduction: short‐ and long‐term evaluation of a cross–cultural awareness programme
Authors: Hill Miriam E. , Augoustinos Martha
Published: January 2005

The present study reports an evaluation of an applied prejudice reduction intervention. Previous research has indicated that such programmes achieve limited success. The programme evaluated was an in‐house anti‐racist education programme aimed at reducing prejudice towards Aboriginal Australians. The target audience were employees of a large public service organization. Knowledge of, prejudice towards, and stereotyping of Aboriginal Australians were assessed before commencing the programme to establish a baseline. Changes in these variables were assessed immediately after completing the programme, and again 3 months after completing the programme. The programme had pronounced effects immediately after completion: there was a significant increase in knowledge and significant decrease in prejudice and negative stereotyping. However, 3 months later, there was no significant difference to baseline levels of prejudice and stereotyping. Knowledge remained significantly higher than at baseline 3 months after completing the programme. High prejudice participants alone experienced a significant, long‐term decrease in old‐fashioned racism. It is concluded that further research must be done to develop more successful strategies of prejudice reduction and stereotype change that are also applicable to ‘real world’ contexts. Copyright © 2001 John Wiley & Sons, Ltd.
A novel approach for screening discrete variations in organic synthesis
Authors: Carlson Rolf , Carlson Johan , Grennberg Anders
Published: January 2005

In this paper we present a general strategy for screening discrete variations in organic synthesis. The strategy is based upon principal properties, i.e. principal component characterization of the constituents defining the reaction system. The first step is to select subsets of test items from each class of constituents defining the reaction space, i.e. substrates, reagents, solvents, catalysts, etc., so that the selected items from each class cover the properties considered. The second step is to construct a candidate matrix which contains all possible combinations of the items in the subsets. This matrix is a full multilevel factorial design. The third step is to assign a tentative model for the screening experiment and to construct the corresponding candidate model matrix. The fourth step is to select experiments to yield an experimental design that spans the variable space efficiently and that also gives good estimates of the model parameters. We present an algorithm that uses singular value decomposition to select experiments. The proposed strategy is then illustrated with an example of the Fischer indole synthesis. Copyright © 2001 John Wiley & Sons, Ltd.