bluuebunny/crossref_metadata_2025 huggingface dataset:
Suppression of growth factor expression and human vascular smooth muscle cell growth by small interfering RNA targeting EGR‐1
Authors: Fahmy Roger G. , Khachigian Levon M.
Published: December 2006

Smooth muscle cell (SMC) proliferation and migration are key processes that occur in the reparative response to injury after percutaneous coronary intervention and in failed bypass grafts for the treatment of atherosclerosis. In the present study, we generated novel synthetic small interfering RNA (siRNA) molecules targeting the coding region of human early growth response‐1 (EGR‐1) mRNA that attenuate the expression of EGR‐1 and that of fibroblast growth factor‐2 (FGF‐2) and granulocyte‐colony stimulating factor (G‐CSF). These agents suppressed SMC proliferation in a dose‐dependent and non‐toxic manner and blocked SMC regrowth from the wound edge following mechanical injury in vitro. In contrast, the scrambled counterpart did not inhibit SMC proliferation, EGR‐1 protein expression or SMC regrowth after injury. These findings demonstrate that EGR‐1 siRNA can serve as inhibitors of SMC proliferation and wound repair suggesting that these agents may potentially be useful in the control of vascular proliferative disorders. J. Cell. Biochem. 100: 1526–1535, 2007. © 2006 Wiley‐Liss, Inc.
Tumor microenvironment abnormalities: Causes, consequences, and strategies to normalize
Authors: Fukumura Dai , Jain Rakesh K.
Published: December 2006

A solid tumor is an organ‐like entity comprised of neoplastic cells and non‐transformed host stromal cells embedded in an extracellular matrix. The expression of various genes is influenced by interactions among these cells, surrounding matrix, and their local physical and biochemical microenvironment. The products encoded by these genes, in turn, control the pathophysiological characteristics of the tumor, and give rise to the abnormal organization, structure, and function of tumor blood vessels. These abnormalities contribute to heterogeneous blood flow, vascular permeability, and microenvironment. Proliferating tumor cells produce solid stress which compresses blood and lymphatic vessels. As a result of vessel leakiness and lack of functional lymphatics, interstitial fluid pressure is significantly elevated in solid tumors. Each of these abnormalities forms a physiological barrier to the delivery of therapeutic agents to tumors. Furthermore, the metabolic microenvironment in tumors such as hypoxia and acidosis hinder the efficacy of anti‐tumor treatments such as radiation therapy and chemotherapy. A judicious application of anti‐angiogenic therapy has the potential to overcome these problems by normalizing the tumor vessels and making them more efficient for delivery of oxygen and drugs. Combined anti‐angiogenic and conventional therapies have shown promise in the clinic. J. Cell. Biochem. 101: 937–949, 2007. © 2006 Wiley‐Liss, Inc.
Temporal evolution of gene expression in rat carotid artery following balloon angioplasty
Authors: Li Jian‐ming , Zhang Xueqing , Nelson Peter R. , Odgren Paul R. , Nelson Janice D. , Vasiliu Calin , Park Jane , Morris Marvin , Lian Jane , Cutler Bruce S. , Newburger Peter E.
Published: December 2006

The success of vascular intervention including angioplasty, stenting, and arterial bypass remains limited by negative remodeling resulted in lumen restenosis. This study was to characterize the global transcription profile reflecting concurrent events along arterial remodeling and neointima formation in a rat carotid artery balloon‐injury model. Expression profiling of injured and control common carotid arteries on days 4, 7, 14 post‐injury that mark the major pathohistological progression stages of neointimal formation were recorded on high‐density oligonucleotide arrays. A subset of genes from microarray‐based data was further studied using quantitative real time RT‐PCR and in situ hybridization with sequential arterial samples from days 1 to 28 post‐injury. The gene‐encoded proteins were validated with Western blot. Besides temporal induction of a large cluster of genes over‐represented by cell proliferation and macromolecule metabolism gene ontology categories, a fast‐evolving inflammation could be demonstrated by the induction of Tgfb and other anti‐inflammatory genes (e.g., C1qtnf3 (C1q and tumor necrosis factor related protein 3 (predicted))) and a shift from type 1 to 2 helper T cell response. The most significant signature of the induced neointimal profile is enrichment of genes functionally related to angiogenesis and extracellular matrix (ECM) remodeling (e.g., Spp1 (secreted phosphoprotein 1), CD44 (CD44 antigen), and Cxcl12 (chemokine (C‐X‐C motif) ligand 12 (stromal cell‐derived factor 1)). Some of the genes represent stress‐responsive mesenchymal stromal cell cytokines. This study highlighted mesenchymal stromal cell cytokines‐driven inflammatory extracellular matrix remodeling, as target processes for potential clinical therapeutic intervention. J. Cell. Biochem. 101: 399–410, 2007. © 2006 Wiley‐Liss, Inc.
Functional properties and intracellular signaling of CCN1/Cyr61
Authors: Chen Ying , Du Xiao‐Yan
Published: December 2006

CCN1/Cyr61 is a member of the protein family that can be promptly induced by growth factors. CCN1/Cyr61 promotes cell proliferation, adhesion, and differentiation. It plays important roles in angiogenesis and extracellular matrix production. In addition, CCN1/Cyr61 has many potential functions in tumorigenesis, development, embryo implantation, as well as formation of endometriotic lesions. Expression of CCN1/Cyr61 is regulated by a variety of agents including cytokines, growth factors, steroid hormones, and some drugs. These inducers regulate the transcription of CCN1/Cyr61 through several signaling transduction pathways. CCN1/Cyr61 is able to interact either with the cell itself or the surrounding cells through an autocrine–paracrine mechanism. It has been reported that CCN1/Cyr61 exerts its functions via interacting with at least five integrins as well as heparan sulfate proteoglycan. By activating Wnt, NF‐kappaB, or tyrosine kinase signaling pathways, CCN1/Cyr61 is not only able to control the growth of epithelial cells and fibroblasts, but also induce or suppress apoptosis in a cell type‐specific manner. J. Cell. Biochem. 100: 1337–1345, 2007. © 2006 Wiley‐Liss, Inc.
Microenvironmental influences in melanoma progression
Authors: Lee John T. , Herlyn Meenhard
Published: December 2006

An often overlooked facet of tumor biology research is the involvement of the surrounding tumor microenvironment. Increasing evidence is being presented to support a major role for stromal components in all stages of tumorigenesis including initiation, progression, and metastasis. Melanoma serves as a model for studying cellular and stromal interactions within the tumor microenvironment due to the array of cell types localized to these lesions. Here, we discuss the both the molecular mechanisms, as well as the extracellular and contextual input that contribute to melanoma progression. Special emphasis is given to the assorted cell types and their interactions with the extracellular matrix and adjacent cells. Melanoma progression also initiates development of intralesional hypoxic regions; the relative significance of hypoxia in disease is also addressed. Lastly, a number of laboratories are currently developing innovative strategies to study melanoma within a microenvironmental platform. These promising model systems and their potential for closing current gaps in knowledge of disease are reviewed. The development of such models holds translational value that cannot be achieved with most current systems. J. Cell. Biochem. 101: 862–872, 2007. © 2006 Wiley‐Liss, Inc.
Benzyl butyl phthalate influences actin distribution and cell proliferation in rat Py1a osteoblasts
Authors: Agas Dimitrios , Sabbieti Maria G. , Capacchietti Mariolina , Materazzi Stefano , Menghi Giovanna , Materazzi Giovanni , Hurley Marja M. , Marchetti Luigi
Published: December 2006

We previously reported that transient administration of phthalates induced actin cytoskeleton disruption in Py1a osteoblasts. However, the mechanism of this transient effect was not elucidated. In this study we provided evidence that the actin cytoskeletal re‐established conditions are dependent on new actin expression and synthesis. To assess the role of phthalates in modulating the distribution of actin, confocal and electron microscopy studies were carried out. Results indicated a modification of actin distribution after phthalate administration. In addition, a relation with the nucleoskeletal component lamin A supports the hypothesis that phthalates may participate in regulatory cell processes involving actin in Py1a osteoblasts. The present study also supports the mitogenic effects of phthalates, which involve microfilament disruption, nuclear actin and lamin A. In particular, the increased levels of cyclin D3, which in mammalian cells plays a critical role in G1 to S transition and is a putative proto‐oncogene in benzyl butyl phthalate treated cells, suggested a possible effect of the endocrine disruptor in cancer processes. J. Cell. Biochem. 101: 543–551, 2007. © 2006 Wiley‐Liss, Inc.
In vitro multipotentiality and characterization of human unfractured traumatic hemarthrosis‐derived progenitor cells: A potential cell source for tissue repair
Authors: Lee Sang Yang , Miwa Masahiko , Sakai Yoshitada , Kuroda Ryosuke , Matsumoto Tomoyuki , Iwakura Takashi , Fujioka Hiroyuki , Doita Minoru , Kurosaka Masahiro
Published: December 2006

Mesenchymal progenitor cells (MPCs) are a very attractive tool in the context of repair and regeneration of musculoskeletal tissue damaged by trauma. The most common source of MPCs to date has been the bone marrow, but aspirating bone marrow from the patient is an invasive procedure. In an attempt to search for alternative sources of MPCs that could be obtained with minimal invasion, we looked into traumatic hemarthrosis of the knee. In this study, we determined whether a population of multipotent MPCs could be isolated from acute traumatic knee hemarthrosis in the absence of intra‐articular fractures. Mononuclear cells were isolated from the aspirated hemarthrosis by density gradient separation, and cultured. We were able to obtain plastic adherent fibroblast‐like cells from the mononuclear cell fractions. Flow cytometry analysis revealed that the adherent fibroblast‐like cells were consistently positive for CD29, CD44, CD105, and CD166, and were negative for CD14, CD34, and CD45. These were similar to control bone marrow stromal cells. These cells could differentiate in vitro into osteogenic, adipogenic, and chondrogenic cells in the presence of lineage‐specific induction factors. In conclusion, acute unfractured traumatic hemarthrosis of the knee contains MPCs with multipotentiality. Because knee hemarthrosis is easy to harvest with minimal pain and without unnecessary invasion, we regard hemarthrosis‐derived cells as an additional progenitor cell source for future tissue engineering and cell‐based therapy in knee injuries. J. Cell. Physiol. 210: 561–566, 2007. © 2006 Wiley‐Liss, Inc.
Enhanced gene expression through temperature profile‐induced variations in molecular architecture of thermoresponsive polymer vectors
Authors: Lavigne Matthieu D. , Pennadam Sivanand S. , Ellis James , Yates Laura L. , Alexander Cameron , Górecki Dariusz C.
Published: December 2006

Background

Successful non‐viral gene targeting requires vectors to meet two conflicting needs—strong binding to protect the genetic material during transit and weak binding at the target site to enable release. Responsive polymers could fulfil such requirements through the switching of states, e.g. the chain‐extended coil to chain‐collapsed globule phase transition that occurs at a lower critical solution temperature (LCST), in order to transport nucleic acid in one polymer state and release it in another.

Methods

The ability of new synthetic polycations based on poly(ethylenei‐ mine) (PEI) with grafted neutral responsive poly(N‐isopropylacrylamide) (PNIPAm) chains to condense DNA into particles with architectures varying according to graft polymer LCST was assessed using a combination of fluorescence spectroscopy, dynamic light scattering (DLS), zeta sizing, gel retardation and atomic force microscopy studies. Transfection assays were conducted under experimental conditions wherein the polymer components were able to cycle across their LCST.

Results

Two PEI‐PNIPAm conjugate polymers with different LCSTs displayed coil‐globule transitions when complexed to plasmid DNA, leading to variations in molecular architecture as shown by changes in emission maxima of an environment‐sensitive fluorophore attached to the PNIPAm chains. Gel retardation assays demonstrated differences in electrophoretic mobilities of polymer‐DNA complexes with temperatures below and above polymer LCSTs. Atomic force micrographs showed changes in the structures of polymer‐DNA complexes for a polymer undergoing a phase transition around body temperature but not for the polymer with LCST outside this range. Transfection experiments in C2C12 and COS‐7 cells demonstrated that the highest expression of transgene occurred in an assay that involved a ‘cold‐shock’ below polymer LCST during transfection.

Conclusions

Designed changes in thermoresponsive polycation vector configuration via temperature‐induced phase transitions enhanced transgene expression. The results indicate that changes in molecular architecture induced by a carefully chosen stimulus during intracellular trafficking can be used to enhance gene delivery. Copyright © 2006 John Wiley & Sons, Ltd.
The nutritive value of egg by‐products and their potential bactericidal activity: in vitro and in vivo studies
Authors: Schmidt Lisa D , Blank Gregory , Boros Danuta , Slominski Bogdan A
Published: December 2006

Technical‐grade egg albumen (TA) and whole egg (WE) by‐products are produced in substantial quantities by egg‐breaking facilities across North America. TA and WE products are recovered during processing but are not approved for human consumption. Both products are known to be rich in fat, maternal antibodies, protein and lysozyme, a bactericidal enzyme. The objective of this research was to explore the potential for egg by‐products to be used as a valuable protein, energy and bactericidal supplement in animal nutrition. To improve the nutritive value of TA and WE, spray‐dried samples were heat treated at various temperatures and their digestible protein content was determined in vitro using a pepsin/pancreatin digestion/dialysis system. In addition, enhancement of lysozyme activity towards Gram‐negative bacteria (GNB) by heat or irradiation was examined. Optimal protein digestibility for TA averaged 80% following heat treatment at 105–110 °C for 10 min. In contrast, protein digestibility of spray‐dried TA was only 55%. Heat treatment (100–122 °C) of spray‐dried WE or hot room storage of spray‐dried TA and WE products at 70 °C for up to 14 days had a minimal effect on protein digestibility in vitro. Heat treatment or γ‐irradiation of lysozyme for at least 20 min at 80 °C or 0.5 kGy, respectively, increased antimicrobial activity towards GNB. When compared with either the heat or radiation control treatments, reductions in Escherichia coli and Salmonella enterica serovar Typhimurium populations increased by at least 1 and 0.5 log10, respectively. In contrast, the effect of irradiation (2 kGy) on the antimicrobial activity of spray‐dried TA was less pronounced. In a feeding trial, rats fed spray‐dried TA and spray‐dried TA subjected to either radiation (1.8 kGy) or heat (80 °C, 20 min) treatment exhibited a body weight gain and protein utilisation equal to or higher than the control (casein diet). In contrast, feeding spray‐dried WE or TA and WE previously maintained in a hot room (70 °C) for 3 days had a negative effect on rat growth and protein utilisation. In the case of WE products this was substantiated by poor digestibility of essential amino acids, including lysine, threonine and, to some extent, methionine. When compared with the control treatments, inclusion of heat‐treated or irradiated TA in the rat diets reduced the population of Enterobacteriaceae. Copyright © 2006 Society of Chemical Industry
Glycogen debranching enzyme and some other factors relating to post‐mortem pH decrease in poultry muscles
Authors: Ylä‐Ajos Maria , Ruusunen Marita , Puolanne Eero
Published: December 2006

The objective of this study was to investigate the activity of glycogen debranching enzyme (GDE, EC 3.2.1.68) in chicken pectoralis superficialis (PS) and quadriceps femoris (QF) muscle post‐mortem. In addition, some other factors relating to pH decrease, such as the activity of glycogen phosphorylase (EC 2.4.1.1) and glycolytic potential were studied. Enzyme activities, glycogen content and lactate content were measured in Ross breed broiler chicken muscles obtained 25 min after stunning. An interesting discrepancy in the activities of the two glycogen degrading enzymes, GDE and phosphorylase, between muscles was found. In light PS muscle, phosphorylase activity was higher (P < 0.001), but GDE activity was lower (P < 0.001) than in dark QF muscle. Buffering capacity and glycolytic potential were higher in PS muscle than in QF muscle. The possible need for high buffering capacity and low GDE activity in PS muscle to protect living muscle from rapid pH decrease was discussed. GDE, together with glycolytic potential, accounted for 40% of the variation in ultimate pH in QF muscle and 61% in PS muscle. Considering the low activity of GDE together with the high activity of phosphorylase found in both muscles, the results of the present study support the hypothesis that GDE may restrict the rate of glycogen degradation. Copyright © 2006 Society of Chemical Industry
Ultrasound‐assisted extraction of ginsenosides in supercritical CO2 reverse microemulsions
Authors: Luo Denglin , Qiu Taiqiu , Lu Qun
Published: December 2006

Ultrasound‐assisted extraction of ginsenosides from ginseng in supercritical CO2 reverse microemulsions formed by bis(2‐ethylhexyl) sodium sulfosuccinate (AOT) was studied. Prior to extraction the ginseng was soaked in water for 12 h. It was found that ultrasound significantly enhanced supercritical CO2 reverse microemulsion extraction. The ginsenoside extraction yield from supercritical CO2 reverse microemulsion with ultrasound of 20 kHz, 15.2 W cm−2 and 3/6 s was 2.63 times that without ultrasound at 24 MPa extraction pressure, 45 °C extraction temperature, 4 h extraction time, 5 MPa separation pressure, 55 °C separation temperature and 2 L h−1 CO2 flow rate with 140 mL of 0.07 mol L−1 AOT/ethanol. The maximum extraction yields of ginsenosides from different concentrations of reverse microemulsions were obtained at different ultrasonic intensities. The extraction yield with 20 kHz ultrasound was higher than that with 38 kHz ultrasound at suitably low intensity; however, it was lower at high intensity. The yield improvement may be basically attributed to the mechanical and thermal effects of ultrasound. Copyright © 2006 Society of Chemical Industry
Effects of heat treatment on the quality and storage life of sweet potato
Authors: Hu Wenzhong , Tanaka Shun‐Ichiro
Published: December 2006

The effects of heat treatment (50 °C) on the sprouting inhibition and spoilage of sweet potato roots (curing temperature: 29 °C) stored in wrapper‐type cold store (WTCS) were determined during year‐long storage. The quality attributes of sweet potato were also evaluated. The results indicated that hot water treatment significantly inhibited sprouting and decay of sweet potato for the storage period. It also showed that there were no significant differences in starch properties in terms of pasting properties, enthalpy and temperatures onset (TO), peak (TP) and endset (TE) of gelatinisation of sweet potato starches among all the treatments, especially between heat‐treated and without‐heat‐treated samples. Also, hot water treatment did not have any significant impact on the internal components' quality of the roots: less than 4% of the year‐long stored roots were discarded due to spoilage. Heat treatment supplied a lethal dose of heat to surface pathogens and cauterised the eyes without damaging the nutritional and processing qualities of sweet potato. The success of storage experiments in prolonging sweet potato stored in WTCS by heat treatment was obtained from the effective control of weight loss, sprouting and decay without influence on quality characteristics. This new technique opens a new avenue to prolonging the storage life of sweet potato with good quality and minimal loss. Copyright © 2006 Society of Chemical Industry
Effect of Lactobacillus cultures on microbiological, chemical and odour changes during storage of rainbow trout fillets
Authors: Katikou Panagiota , Ambrosiadis Ioannis , Georgantelis Dimitrios , Koidis Pavlos , Georgakis Spyridon A
Published: December 2006

The purpose of this study was to investigate the effect of applying two Lactobacillus protective cultures on microbiological, chemical and odour changes during storage of refrigerated vacuum‐packed rainbow trout (Oncorrynchus mykiss) fillets. Lactobacillus sakei CECT 4808 and Lb. curvatus CECT 904T were inoculated individually or in combination into rainbow trout fillets. The samples were vacuum‐packed and stored at 4 ± 0.5 °C and were assessed during a 20‐day storage period for microbiological (Enterobacteriaceae, Pseudomonas spp., lactic acid bacteria (LAB), H2S‐producing bacteria, yeasts and moulds) and chemical (pH, total volatile basic nitrogen, lipid oxidation) parameters and off‐odour. Samples inoculated with Lb. sakei and with both strains had significantly (P≤0.05) lower counts of all microbiological spoilage indicator organisms (Enterobacteriaceae, Pseudomonas spp., H2S‐producing bacteria, yeasts and moulds) than those inoculated with Lb. curvatus or the controls. All chemical parameters examined and off‐odour scores were also significantly (P≤0.05) improved in the samples inoculated with Lb. sakei or with both strains compared with those inoculated with Lb. curvatus or the controls. Lb. sakei generally showed a better preservative effect (P≤0.05) than the combination of strains. Inoculation with Lb. sakei CECT 4808 could provide an additional hurdle to improve shelf‐life of refrigerated vacuum‐packaged trout fillets, as inoculation with this strain resulted in extension of shelf‐life by 5 days. Furthermore, this strain showed some antioxidative ability, which could retard lipid oxidation in fish. Copyright © 2006 Society of Chemical Industry
Structural and conformational analysis of two native procyanidin trimers
Authors: Tarascou Isabelle , Ducasse Marie‐Agnès , Dufourc Erick J. , Moskau Detlef , Fouquet Eric , Laguerre Michel , Pianet Isabelle
Published: December 2006

The structure and conformation of two native procyanidin trimers in water have been determined using 2D NMR and molecular mechanics. The results show the existence of four rotameric forms, one of which is predominant (60 to 80%). These four rotamers are shown to be in slow to intermediate exchange on the NMR timescale. Both trimers, whose structures vary owing to a different substitution of one carbon atom, adopt conformations in which stacking between different phenolic rings is favored. Copyright © 2006 John Wiley & Sons, Ltd.
Three‐dimensional NMR Spectroscopy of organic molecules by random sampling of evolution time space and multidimensional Fourier transformation
Authors: Misiak Maria , Koźmiński Wiktor
Published: December 2006

In this communication we present the application of a new method, which enables one to acquire 3D NMR spectra in a reasonable time and preserves high resolution in indirectly detected domains. The new method is based on random distribution of time domain data points followed by Quaternion FT with respect to two time variables in one step.

The experimental examples include three‐dimensional spectra of strychnine in CDCl3, TOCSY‐HSQC, COSY‐HMBC, and the new technique proposed here: heteronuclear single quantum multiple bond correlation (HSQMBC). The obtained spectra are compared to those recorded at the same time employing the conventional acquisition scheme. We show that high‐quality 3D spectra of organic compounds can be obtained in reasonable experimental time and that they are of great interest in cases when direct analysis of 2D spectra is difficult. Copyright © 2006 John Wiley & Sons, Ltd.
Apparent diffusion coefficient of the prostate in men prior to biopsy: determination of a cut‐off value to predict malignancy of the peripheral zone
Authors: Kumar Virendra , Jagannathan N. R. , Kumar Rajeev , Thulkar S. , Gupta S. Dutta , Dwivedi S. N. , Hemal A. K. , Gupta N. P.
Published: December 2006

Determination of the apparent diffusion coefficient (ADC) of the prostate in men (n = 60) with raised prostate‐specific antigen (PSA) or an abnormal digital rectal examination (DRE) prior to transrectal ultrasound (TRUS) guided biopsy using endorectal DWI is reported. Patients were categorized into different groups based on their PSA levels. The mean ADC was calculated from a number of regions of interest (ROIs) for the whole of the peripheral zone (PZ) and the central gland (CG). A total of 1108 ROIs were analyzed from 60 patients. The mean ADC value of the PZ was higher than that of the CG in controls. A total of 23 out of 60 patients were positive for malignancy on biopsy, and the mean ADC of the PZ was lower in these patients compared with those who were negative. Moreover, the mean ADC obtained for the whole of the PZ of the prostate in different groups of patients and controls showed a decreasing trend. A plot between PSA and mean ADC for the PZ showed non‐linear association with logarithmic decrease in ADC. The mean ADC of the CG was not significantly different in patients who were positive or negative for malignancy in biopsy. In addition, a cut‐off value of 1.17 × 10−3 mm2/s (sensitivity = 73% and specificity = 74%, area under the curve = 0.83) for the mean ADC for the whole of the PZ of patients was determined by using the receiver operating characteristic curve (ROC) to predict malignancy of the PZ. Copyright © 2006 John Wiley & Sons, Ltd.
A simple mechanism for stabilizing network queues in TCP/IP networks
Authors: Aweya James , Ouellette Michel , Montuno Delfin Y.
Published: December 2006

In this paper we determine the stability bounds for the DRED active queue management (AQM) algorithm using a previously developed nonlinear dynamic model of TCP. We develop a second‐order linear model with time delay by linearizing the nonlinear model. Using the Pade approximation of time‐delayed systeme−R0s, whereR0is the delay in the system, we then determine the range of stabilizing gains of DRED when controlling the second‐order system with time delayR0. We also present examples showing the stability bounds of the DRED controller gain for networks with different parameters such as link capacity, load level, and round‐trip time. In addition, we describe an efficient implementation of the DRED AQM algorithm. Copyright © 2006 John Wiley & Sons, Ltd.
Numerical exploration of flow topology and vortex stability in a curved duct
Authors: Tsai S. F. , Sheu Tony W. H.
Published: December 2006

We performed incompressible flow simulation in a square duct with 90° bend and a curvature radius of 2.3 to extend our understanding of the vortical flow development in the bend. The solutions for the flow investigated at the Reynolds number of Re=790 are obtained in a tri‐quadratic element system, where velocities stagger the pressure working variable, using the streamline‐upwind finite element model and the BiCGSTAB iterative solver. The simulated results reveal that centrifugal force convects the quickly moving fluid particles towards the outer wall. The axial velocity, as a result, shows twin peaks in the curved channel. At about θ=66°, the secondary flow shows three complex pairs of vortices. Also noteworthy is the formation of a downstream spiralling flow motion. To better elucidate the dominating three‐dimensional flow nature, the topological study of limiting streamlines was undertaken. Insight into the longitudinal flow instability is gained by tracking the formation and diminishing of limiting cycles. Copyright © 2006 John Wiley & Sons, Ltd.
The significance of LMO2 expression in the progression of prostate cancer
Authors: Ma S , Guan XY , Beh PSL , Wong KY , Chan YP , Yuen HF , Vielkind J , Chan KW
Published: December 2006

LIM domain only 2 (LMO2) proteins are important regulators in determining cell fate and controlling cell growth and differentiation. This study has investigated LMO2 expression in human prostatic tissue specimens, prostate cancer cell lines, and xenografts; and has assessed the possible role and mechanism of LMO2 in prostate carcinogenesis. Immunohistochemical analysis on a tissue microarray consisting of 91 human prostate specimens, including normal, prostatic hyperplasia, high‐grade prostatic intraepithelial neoplasia, and invasive carcinoma, revealed that overexpression of LMO2 was significantly associated with advanced tumour stage, as measured by Gleason score (p = 0.012), as well as with the development of distant metastasis (p = 0.018). These data were supported by quantitative real‐time PCR experiments, where LMO2 mRNA levels were found to be significantly higher in prostate tumour specimen than in normal epithelium (p = 0.037). The expression of LMO2 in cell lines and xenografts representing androgen‐dependent (AD) and androgen‐independent (AI) prostate cancer stages was further studied. Consistent with the in vivo data, LMO2 mRNA and protein were found to be overexpressed in the more aggressive AI cells (PC3, DU145, and AI CWR22 xenografts) compared with less aggressive AD cells (LNCaP and AD CWR22 xenografts). Furthermore, stable introduction of LMO2 into LNCaP cells conferred enhanced cell motility and invasiveness in vitro, accompanied by down‐regulation of E‐cadherin expression. Taken together, these findings provide the first evidence to support the hypothesis that LMO2 may play an important role in prostate cancer progression, possibly via repression of E‐cadherin expression. Copyright © 2006 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Antazida – Ein historischer Überblick: Konstanz und Wandel im Lauf der Jahrhunderte
Authors: Meyer Wolfgang
Published: December 2006

Mineralische antazide Arzneistoffe wurden über Jahrtausende hinweg zur Behandlung von gastrointestinalen Beschwerden eingesetzt. Doch erst mit der Entdeckung der Magensäure zu Beginn des 19. Jahrhunderts erfolgte eine intensivere Erforschung dieser Substanzklasse. Antazida waren dann fast 200 Jahre lang eine der wichtigsten Stützen in der konservativen Ulkustherapie. Einen Höhepunkt markiert die von Sippy nach dem Ersten Weltkrieg entwickelte Hochdosistherapie. Vor ca. 30 Jahren begann sich jedoch das Bild zu ändern. Mit der Einführung der H2‐Rezeptorantagonisten schwand die Bedeutung der Antazida, obwohl im direkten klinischen Vergleich ihre therapeutische Gleichwertigkeit gezeigt und auch neue pharmakologische Eigenschaften belegt werden konnten. Man sprach sogar von einer Renaissance der Antazida. Durch die Entdeckung von Helicobacter pylori und die Einführung der Protonenpumpenhemmer vor ca. 20 Jahren wurden die Antazida bei der Primärbehandlung des Ulcus ventriculi et duodeni und der gastro‐ösophagealen Refluxkrankheit indes endgültig in den Hintergrund gedrängt. Gleichwohl spielen sie in der Selbstmedikation auch heute noch eine bedeutende Rolle.
Medizinische Chemie von Histamin‐H2‐Rezeptorantagonisten: Klassische Wirkstoffentwicklung
Authors: Kubas Holger , Stark Holger
Published: December 2006

Cimetidin war der erste therapeutisch eingesetzte “Säureblocker” und revolutionierte vor etwa 30 Jahren die Therapie peptischer Erkrankungen. Über systematische und rationale Optimierungsstrategien werden die Wege zum ersten Wirkstoff mit Marktreife und zu weiteren Entwicklungen aufgezeigt. Hierbei spielen Affinität, Bioverfügbarkeit und Interaktionen besondere Rollen.
Antazida – effizient und preiswert: Einfache anorganische Verbindungen mit großer Wirkung
Authors: Wagner Matthias
Published: December 2006

Vor allem bei Sodbrennen und säurebedingten Magenbeschwerden, also den häufigsten Krankheitsbildern des oberen Gastrointestinaltraktes, gelten Antazida auch heute noch als geeignete Arzneimittel. Die in diesem Artikel beschriebenen Nebenwirkungen bergen bei einer adäquaten Therapie mit Antazida kein hohes Gefahrenpotenzial, sondern sind nur dann zu befürchten, wenn außergewöhnliche Umstände im Sinne einer pathologischen Resorption und/oder einer gestörten Elimination die Pharmakokinetik der Antazida beeinflussen. Generell sind Antazida nach allgemeiner Überzeugung gut verträglich, da ihr hauptsächlicher Wirkort nicht systemisch ist.
Antazida und H2‐Antihistaminika bei Hyperazidität: Wissenswertes zu Nebenwirkungen und Interaktionen
Authors: Wegat Tanja , Metzman Katrin , Leuner Kristina , Müller Walter E.
Published: December 2006

Der Einsatz von Antazida und H2‐Blockern in der Selbstmedikation des Sodbrennens stellt den Apotheker vor die Aufgabe, unter den OTC‐Produkten ein passendes Präparat auszuwählen. Im Bedarfsfall sollte die Abklärung einer Refluxösophagitis oder Ulkuserkrankung durch den Arzt erfolgen. Wie die Therapie im Hinblick auf Verträglichkeit, Interaktionen und Einnahmemodalitäten am besten unterstützt werden kann, soll dieser Beitrag kurz zusammenfassen.
Selbstmedikation mit Antazida und H2‐Antihistaminika. Was tun bei Sodbrennen und Co.?
Authors: Martin Eric
Published: December 2006

Mittel zur Behandlung von Sodbrennen spielen in der Selbstmedikation traditionell eine bedeutsame Rolle. Mit Antazida und H2‐Antihistaminika stehen zwei Gruppen von Wirkstoffen zur Verfügung, deren Wirksamkeit und Risikoprofil gut eingeschätzt werden können und die folglich ein hohes Maß an Sicherheit für die Selbstmedikation bringen. Unerwünschte Arzneimittelwirkungen sind in der Regel gutartig, mögliche Wechselwirkungen einschlägig bekannt und als solche meist gut vermeidbar. Substanzielle Risiken können indessen von einem unkritischen oder nicht indizierten Einsatz herrühren, von einer Verschleppung einer ärztlichen Diagnosestellung bzw. einer Maskierung schwerwiegender Erkrankungen. Insofern ist der Patient ohne jede Einschränkung auf eine sorgfältige Beratung und Betreuung angewiesen.
Humanisierte Hefen
Authors: Winckler Thomas
Published: December 2006

Können wir demnächst komplex N‐glycosylierte Proteinwirkstoffe statt in Säugerzellen wesentlich billiger in Hefen produzieren?
B‐type natriuretic peptide as a marker for cardiac dysfunction in anthracycline‐treated children
Authors: Aggarwal Sanjeev , Pettersen Michael D. , Bhambhani Kanta , Gurczynski Joellyn , Thomas Ronald , L'Ecuyer Thomas
Published: December 2006

Background

Anthracyclines (AC) are useful antineoplastic agents, whose utility is limited by progressive cardiotoxicity. Our purpose was to evaluate plasma B‐type natriuretic peptide (BNP), as a screening test for detecting late cardiac dysfunction in AC‐treated children and to determine the prevalence of late cardiac dysfunction at low cumulative AC doses.

Materials and Methods

This was a prospective study in which patients who had completed AC therapy at least 1 year earlier, underwent a detailed echocardiogram and a simultaneous BNP level. Cardiac dysfunction was defined as any one of the following: shortening fraction (FS) <29%, rate corrected velocity of circumferential fiber shortening (VCFc) <0.9 c·sec−1, end systolic wall stress (ESWS) >60 g·cm−2, abnormal VCFc: ESWS ratio or decreased mitral inflow velocity (E/A) ratios, compared to age‐specific norms.

Results

The cohort (n = 63) included 37 males with a median age of 13.1 years (range, 6.5–26.5 years). Cardiac dysfunction was found in 26 (41%) patients and in 40% of patients who received cumulative doses <150 mg·m−2. ESWS was the most common abnormality. Mean BNP levels in the subset with abnormal function were significantly higher than the normal group (23.4 ± 25.3 vs. 14.2 ± 8.9 pg·ml−1, P = 0.02).

Conclusions

Plasma BNP was significantly elevated in AC‐treated patients with late cardiac dysfunction, although there was considerable overlap of levels between groups with and without cardiac dysfunction. BNP may need further evaluation as a serial index of cardiac function in this population. Cardiac dysfunction was observed in a significant proportion of patients, even at low cumulative AC doses. Pediatr Blood Cancer 2007;49:812–816. © 2006 Wiley‐Liss, Inc.
Use of complementary and alternative medicine in children with cancer in Occidental, Mexico
Authors: Gomez‐Martinez Ricardo , Tlacuilo‐Parra Alberto , Garibaldi‐Covarrubias Roberto
Published: December 2006

Purpose

To describe the types of complementary and alternative medicine (CAM) used by pediatric cancer patients attending a tertiary care hospital in Western Mexico.

Patients and Methods

In a cross‐sectional survey, parents were interviewed and types of CAM employed as well as factors related to their use and their perceived effectiveness were determined.

Results

One hundred ten parents of pediatric cancer patients completed the survey. Seventy‐seven patients (70%) received CAM. Of CAM used, herbal remedies (69%) and orally administered products (26%) were most common. Mean number of therapies was 2 ± 1.1 (95% CI 1.59–2.12). Prior CAM use by the family was associated with use in patients (P = 0.006) (OR 4.6, CI 95% 1.7–12.9). Perceived usefulness was reported in 79% of CAM users.

Conclusion

CAM use in Mexican children is common, most frequently with herbal therapies. The majority perceived benefits with its usage but in most cases, the treating physician was not informed about this practice. Pediatr Blood Cancer 2007;49:820–823. © 2006 Wiley‐Liss, Inc.
Splenectomy in children with idiopathic thrombocytopenic purpura: A prospective study of 134 children from the Intercontinental Childhood ITP Study Group
Authors: Kühne Thomas , Blanchette Victor , Buchanan George R. , Ramenghi Ugo , Donato Hugo , Tamminga Rienk Y.J. , Rischewski Johannes , Berchtold Willi , Imbach Paul
Published: December 2006

Background

Splenectomy is an effective procedure for children and adults with severe or refractory idiopathic thrombocytopenic purpura (ITP). Data regarding pediatric patients are limited.

Procedure

Sixty‐eight Intercontinental Childhood ITP Study Group (ICIS) investigators from 57 institutions in 25 countries participated in a splenectomy registry. Data from 153 patients were submitted, of whom 134 had a splenectomy and were analyzed.

Results

The median age at splenectomy was 11.8 (2.7–20.7) years. The median postsplenectomy follow‐up was 2.0 (0.1–4.5) years. Pre‐splenectomy vaccination was not administered in 21 children (15.7%). Open and laparoscopic splenectomy procedures were performed in 67 and 65 evaluable children, respectively. Surgical technique was not reported in two children. Overall immediate platelet response to splenectomy was achieved in 113 patients (86.3%). Eighty percent of responders maintained their status of response during the following 4 years. Older age, longer duration of ITP, and male gender correlated with a complete response. Post‐splenectomy sepsis was reported in seven patients without lethal outcome, although sepsis might be differently defined at participating institutions.

Conclusions

Splenectomy is effective in children with ITP. Management varies greatly in different institutions. These Registry data may serve as a basis for future clinical trials to assess the indication and timing of splenectomy. Pediatr Blood Cancer 2007;49:829–834. © 2006 Wiley‐Liss, Inc.
Genetic susceptibility and body mass in childhood cancer survivors
Authors: Ross Julie A.
Published: December 2006

Childhood cancer survivors are at increased risk of many long‐term treatment‐related sequel such as second cancers, cardiovascular disease, and pulmonary complications. Certain treatments seem to influence the risk of becoming overweight, obese, or underweight, and abnormal body mass index (BMI) is associated with increased morbidity and mortality. Because BMI is modifiable, it is important to identify treatment and patient‐related factors contributing to altered BMI. New research areas include exploring how genetic susceptibility through population polymorphism may contribute to BMI. Illuminating potential gene–environment interactions that influence obesity and underweight might be more readily accomplished in a study of high‐risk individuals (i.e., childhood cancer survivors) with well‐characterized exposures. The new Childhood Cancer Research Network in the Children's Oncology Group, when fully implemented, should make it less difficult in the future to recruit the large numbers of patients needed for such studies. Pediatr Blood Cancer 2007;48:731–735. © 2006 Wiley‐Liss, Inc.
Essential versus reactive thrombocythemia in children: Retrospective analyses of 12 cases
Authors: El‐Moneim Abeer Abd , Kratz Christian P. , Böll Silke , Rister Manfred , Pahl Heike L. , Niemeyer Charlotte M.
Published: December 2006

Background

Essential thrombocythemia (ET) rarely occurs in the pediatric population and little is known about the clinical course and the molecular characteristics.

Procedure

In this retrospective multi‐institutional study we examine the clinical, hematological, and molecular features of 12 children aged 5–16 years with thrombocytosis and a suspected diagnosis of ET.

Results

Median follow‐up was 59 months (range 10–72). Seven patients presented with clinical symptoms potentially related to thrombocytosis. The remaining five patients were diagnosed incidentally. Median platelet count at diagnosis was 1,325 × 109/L (range 600–3,050). In 11 out of 12 cases bone marrow morphology was consistent with ET, the remaining patient had chronic idiopathic myelofibrosis. Cytogenetic analyses were normal in all studied cases and only one out of nine analyzed cases harbored a JAKV617F allele. Within 6 months after initial presentation one patient who was initially asymptomatic developed thrombosis and another patient had mild bleeding. Eight patients were treated with acetylsalicylic acid, one patient received hydroxyurea, and two patients received anagrelide. At last follow‐up, all patients were alive and none had developed leukemia. Five patients experienced hematological remission. Two children had not received any therapy. During the course of their disease, nine patients developed symptoms possibly attributable to an elevated platelet count.

Conclusions

In JAK2 mutation negative cases, long‐term follow‐up is helpful to distinguish between primary and secondary thrombocytosis. Secondary cases are not associated with organomegaly but may present with unspecific symptoms. Indications for treatment in children remain unclear. Pediatr Blood Cancer 2007;49:52–55. © 2006 Wiley‐Liss, Inc.
Functionalized poly(oxanorbornene)‐block‐copolymers: Preparation via ROMP/click‐methodology
Authors: Kluger Christian , Binder Wolfgang H.
Published: December 2006

Block copolymers on basis of poly(oxanorbornenes) bearing functional moieties in their side‐chains are prepared via a combination of ROMP‐methods and 1,3‐dipolar‐“click”‐reactions. Starting from N‐substituted‐ω‐bromoalkyl‐oxanorbornenes and alkyl‐/perfluoroalkyl‐oxanorbornenes, block copolymers with molecular weights up to 25,000 g mol−1 were generated. Subsequent nucleophilic exchange‐reactions yielded the block‐copolymers functionalized with ω‐azidoalkyl‐moieties in one block. The 1,3‐azide/alkine‐“click” reactions with a variety of terminal alkynes in the presence of a catalyst system consisting of tetrakis(acetonitrile)hexafluorophosphate copper(I) and tris(1‐benzyl‐5‐methyl‐1H‐ [1,2,3]triazol‐4‐ylmethyl)‐amine furnished the substituted block copolymers in high yields, as proven by NMR‐spectroscopy. The resulting polymers were investigated via temperature‐dependent SAXS‐methods, revealing their microphase separated structure as well as their temperature‐dependent behavior. The presented method offers the generation of a large set of different block‐copolymers from only a small set of starting materials because of the high versatility of the “click” reaction, thus enabling a simple and complete functionalization after the initial polymerization reaction. © 2006 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 45: 485–499, 2007
Nanometer‐sized polyradical particles: Organic magnetic dot array formed on a silicon microfabricated substrate
Authors: Tanaka Manabu , Imai Shingo , Tanii Takashi , Numao Yoshiteru , Shimamoto Naonobu , Ohdomari Iwao , Nishide Hiroyuki
Published: December 2006

A magnetically active, purely organic dot array was formed by the selective deposition of polyradical nanoparticles on array‐like‐formed pits on a silicon substrate. The nanometer‐sized polyradical particles, poly(4‐methacryoyloxy‐2,2,6,6‐tetramethylpiperidine‐1‐oxyl), were prepared by the emulsion polymerization of 4‐methacryloyloxy‐2,2,6,6‐tetramethylpiperidine‐1‐acetoxyl followed by a deprotection reaction and oxidation in air. The size (diameter) and radical spin concentration of the polyradical nanoparticles were tunable between the polymerization and oxidation conditions. Electrochemical studies revealed the redox property of the polyradical nanoparticles. The magnetic response image of the polyradical nanoparticles was obtained by magnetic force microscopy, reflecting their radical spin concentrations. These results suggested a possible approach for the use of organic polyradical nanoparticles as organic magnetic dot arrays. © 2006 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 45: 521–530, 2007
Field electroantennogram and trap assessments of aerosol pheromone dispensers for disrupting mating in Epiphyas postvittana
Authors: Suckling David M , Daly John M , Chen Xiong , Karg Gerhard
Published: December 2006

An electronically controlled aerosol system for mating disruption was evaluated against Epiphyas postvittana Walker in apple orchards in New Zealand. The area in which male moths were affected by the aerosol system was examined using catches in traps radiating from a central single‐point source of either one aerosol can dispenser or 100 polyethylene tubing dispensers, compared with catches in orchard plots without pheromone dispensers. Both pheromone dispensing systems decreased moth catch to similar levels at 5–10 m from the central release point, but there was 5.5‐fold more pheromone released from aerosol cans than from polyethylene dispensers over a 24 h period. Trap catches were reduced by about 90% in plots treated with either five aerosol cans per hectare or uniform deployment of polyethylene dispensers. Recordings of electroantennograms in open grassed plots and orchards indicated that the treated cotton pad of an aerosol dispenser and a point source of 100 polyethylene tubing dispensers produced similar electroantennogram recordings. Electroantennogram recordings provided evidence that pheromone plume detection from a single‐point source was maintained over a range of 5–40 m downwind in the orchard. On present evidence, aerosol pheromone dispensers could not be recommended for further testing towards control of E. postvittana under New Zealand conditions owing to their higher cost of purchase and operation. Copyright © 2006 Society of Chemical Industry