bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cyanide bystander effect of the linamarase/linamarin killer‐suicide gene therapy system
Authors: Luisa Cortés Maria , García‐Escudero Vega , Hughes Monica , Izquierdo Marta 
Published: September 2002

AbstractBackgroundThe killer‐suicide system linamarase/linamarin (lis/lin) uses the plant gene linamarase (β‐glucosidase) to convert the cyanogenic glucoside substrate, linamarin, into glucose and cyanide. We have studied the bystander effect associated with this new system mediated by the production of the cyanide ion that diffuses freely across membranes.MethodsImmunofluorescent staining of cells treated with an anti‐linamarase antibody allowed us to localize the enzyme within the cells. Flow cytometry was used to determine the sensitivity of different mixtures of cells, C6lis and C6gfp (green), to linamarin as a percentage of cell survival.ResultsWe demonstrate here that rat glioblastoma C6 cells carrying the linamarase gene (lis), mixed with naive C6 cells and exposed to linamarin, induce generalized cell death. Cells expressing lis efficiently export linamarase, whereas linamarin enters cells poorly by endocytosis; as a result most of the cyanide is produced outside the cells. The study was facilitated by the presence of the green fluorescent protein (gfp) gene in the bystander population. As few as 10% C6lis‐positive cells are sufficient to eliminate the entire cell culture in 96 h.ConclusionsThis bystander mechanism does not preferentially kill toxic metabolite producer cells compared with bystander cells, thus allowing production of sufficient cyanide to cause tumor regression. In this report we confirm the potential of the lis/lin gene therapy system as a powerful tool to eliminate tumors in vivo. Copyright © 2002 John Wiley & Sons, Ltd.
Genetic retargeting of adenovirus vectors: functionality of targeting ligands and their influence on virus viability
Authors: Magnusson Maria K. , See Hong Saw , Henning Petra , Boulanger Pierre , Lindholm Leif 
Published: September 2002

AbstractBackgroundWe studied the ability of adenovirus type 5 (Ad5) to encapsidate new cellular ligands carried by their fibers to yield functional retargeted vectors for gene therapy. Recombinant Ad5 fibers containing shaft repeats 1 to 7 and an extrinsic trimerization motif, and terminated by its native knob or amino acid motifs containing RGD, have been rescued into infectious virions.MethodsPolypeptide ligands of cell surface molecules, including single‐chain antibodies or epidermal growth factor, were cloned into recombinant fibers. Phenotypic analysis of fiber constructs and rescuing into the Ad5 genome were performed. Recombinant viruses were characterized with reference to fiber content, growth rate and infectivity.ResultsA major limiting factor for recovering viable recombinant Ad5 carrying fiber‐fused polypeptide ligands was apparently the ability of the ligand to fold correctly within the cellular cytoplasm. This constraint has previously not been systematically evaluated in the literature. Phenotypic analysis of the fiber‐ligand fusions showed that their degree of cytoplasmic solubility correlated with their ability to yield viable Ad5 vectors. Our results suggested that the fiber manipulations diminish virus growth rate, probably through different, opposing effects: (i) the reduced shaft length increases fiber solubility in the absence of the knob but (ii) diminishes virus entry, and (iii) the absence of the knob alters the overall protein composition of the virion and decreases its fiber copy number.ConclusionsBased on our findings, cytoplasmic solubility and cytoplasmic ligand reactivity of fiber‐ligand fusion proteins are the best prediction criterion for viability and recovery of genetically retargeted Ad vectors. Copyright © 2002 John Wiley & Sons, Ltd.
Antisense MBD2 gene therapy inhibits tumorigenesis
Authors: Slack Andrew , Bovenzi Veronica , Bigey Pascal , Ivanov M. A. , Ramchandani Shyam , Bhattacharya Sanjoy , tenOever Benjamin , Lamrihi B. , Scherman Daniel , Szyf Moshe 
Published: September 2002

AbstractBackgroundAberration in the pattern of DNA methylation is one of the hallmarks of cancer. We present data suggesting that dysregulation of MBD2, a recently characterized member of a novel family of methylated DNA binding proteins, is involved in tumorigenesis. Two functions were ascribed to MBD2, DNA demethylase activity and repression of methylated genes.MethodsMultiple antisense expression and delivery systems, transfection, electrotransfer and adenoviral were employed to demonstrate that MBD2 is essential in tumorigenesis, both ex vivo and in vivo.ResultsInhibition of MBD2 by antisense expression resulted in inhibition of anchorage‐independent growth of antisense transfected cancer cells or cells infected with an adenoviral vector expressing MBD2 antisense. Xenograft tumors treated with an adenoviral vector expressing MBD2 antisense or xenografts treated with electrotransferred plasmids expressing MBD2 antisense showed reduced growth.ConclusionsThese results support the hypothesis that one or both of the functions described for MBD2 are critical in tumorigenesis and that MBD2 is a potential anticancer target. Copyright © 2002 John Wiley & Sons, Ltd.
Development and characterization of a minimal inducible packaging cell line for simian immunodeficiency virus‐based lentiviral vectors
Authors: Kuate Seraphin , Wagner Ralf , Überla Klaus 
Published: September 2002

AbstractBackgroundLentiviral vectors allow gene transfer into non‐dividing cells. Further development of these vector systems requires stable packaging cell lines that enable adequate safety testing.MethodsTo generate a packaging cell line for vectors based on simian immunodeficiency virus (SIV), expression plasmids were constructed that contain the codon‐optimized gag‐pol gene of SIV and the gene for the G protein of vesicular stomatitis virus (VSV‐G) under the control of an ponasterone‐inducible promoter. Stable cell lines expressing these packaging constructs were established and characterized.ResultsThe RT activity and vector titers of cell clones stably transfected with the inducible gag‐pol expession plasmid could be induced by ponasterone by more than a factor of 1000. One of these clones was subsequently transfected with the ponasterone‐inducible VSV‐G expression plasmid to generate packaging cells. Clones of the packaging cells were screened for vector production by infection with an SIV vector and subsequent induction by ponasterone. In the supernatant of selected ponasterone‐induced producer clones vector titers of more than 1×105 transducing units/ml were obtained. Producer cell clones were stable for at least five months, as tested by vector production.ConclusionsThe packaging cells described should be suitable for most preclinical applications of SIV‐based vectors. By avoiding regions of high homology between the vector and the packaging constructs, the design of the SIV packaging cell line should reduce the risk of transfer of packaging genes to target cells and at the same time provide flexibility with respect to the SIV vector constructs that can be packaged. Copyright © 2002 John Wiley & Sons, Ltd.
Constructing representations of Karl Spencer Lashley
Authors: Dewsbury Donald A. 
Published: September 2002

AbstractI compare, contrast, and analyze two published constructions, a straightforward approach and a social constructivist perspective, of the life and work of psychobiologist Karl S. Lashley (1890–1958). Although it is clear at a general level that scientific endeavors are affected by extrascientific factors, particular concern is directed at the issues involved in demonstrating that the scientific work of an individual, in this case Lashley, is affected by specific extrascientific influences. There is insufficient evidence to conclude that Lashley's work was driven predominantly by racial and genetic determinist positions and that he was something other than the scientist he represented himself as being. I then discuss an unpublished personality theory approach to Lashley that suggests the influence of some personality characteristics on his work and helps to provide balance and perspective in constructing representations of Lashley. © 2002 Wiley Periodicals, Inc.
Friedrich Albert Lange on neo‐Kantianism, socialist Darwinism, and a psychology without a soul
Authors: Teo Thomas 
Published: September 2002

AbstractFriedrich Albert Lange was a German philosopher, political theorist, educator, and psychologist who outlined an objective psychology in the 1860s. This article shows how some of the most important worldviews of the nineteenth century (Kantianism, Marxism, and Darwinism) were combined creatively in his thought system. He was crucial in the development of neo‐Kantianism and incorporated psycho‐physiological research on sensation and perception in order to defend Kant's epistemological idealism. Based on a critique of phrenology and philosophical psychology of his time, Lange developed a program of a psychology without a soul. He suggested that only those phenomena that can be observed and controlled should be studied, that psychology should focus on actions and speech, and that for each psychological event the corresponding physical or physiological processes should be identified. Lange opposed introspection and subjective accounts and promoted experiments and statistics. He also promoted Darwinism for psychology while developing a socialist progressive‐democratic reading of Darwin in his social theory. The implications of socialist Darwinism on Lange's conceptualization of race are discussed and his prominence in nineteenth century philosophy and psychology is summarized. © 2002 Wiley Periodicals, Inc.
The role of evidence in interpretations of the scientific work of Karl Lashley
Authors: Dewsbury Donald A. 
Published: September 2002

AbstractI discuss some of the issues underlying the different perspectives of Nadine Weidman and myself on the scientific oeuvre of Karl Lashley. I emphasize that our disagreements concern the kind of evidence needed to support specific claims more than any differences in our models of science. © 2002 Wiley Periodicals, Inc.
Exports, domestic policy and world markets: a panel study
Authors: Love J. , Turner E. 
Published: September 2002

AbstractThis paper analyses how export growth rates in sub‐Saharan Africa are determined by both domestic and external market conditions. We highlight the problems of measuring trade orientation given the various domestically‐determined factors which influence the conditions faced by exporters. Focusing on the impact of trade policy is not a good measure of trade orientation since additional domestic policies can have an important influence on the trade orientation of a country. Hence, we select an index which incorporates the effect of trade and other policies. Then we construct an index which provides a more appropriate measure of conditions faced by exporters in the world market than previously cited measures. We find that, contrary to the recent literature, external market conditions are still critical in explaining export growth rates in sub‐Saharan Africa and should be taken into account when engaging in policy decisions. Copyright © 2001 John Wiley & Sons, Ltd.
Stabex versus IMF compensatory financing: impact on fiscal policy
Authors: Brun Jean‐Francois , Chambas Gérard , Laporte Bertrand 
Published: September 2002

AbstractThe supply of external financing to developing countries generally tends to increase in periods when export earnings are booming and thus, in periods of increasing government revenues. Conversely, Stabex and IMF Compensatory Financing transfers are primarily designed to take place in response to a fall in export earnings, and thus, in periods when government revenues are decreasing. However, these transfers occur in an unsteady way with respect to the cycle of government revenues. When occurring in periods of decreasing government revenues, only Stabex transfers are used to finance additional primary expenditures (i.e. expenditures other than interest on public debt). This effect contrasts with the effects usually reported for other instruments of external financing. In periods of increasing government revenues, Stabex and Compensatory Financing transfers have no impact on fiscal deficit. Copyright © 2001 John Wiley & Sons, Ltd.
Women and war: the role Kuwaiti women played during the Iraqi occupation
Authors: Juliá Maria , Ridha Hadi 
Published: September 2002

AbstractIn many societies, women face a gender bias rooted in feudal socio‐economic relations and religious institutions that justify female subordination (Youseff,1972). Yet, aided by the experience of human rights movements, women have made progress in the past few decades in overcoming a cultural tradition of male domination and superiority. Circumstances of war have also empowered women, allowing them to become active agents in their own development and liberation (Cagan and Juliá,1998). However, movement toward equality or democratization during these conflicts indicate that ‘women's success might be ephemeral, a product of crisis mobilization’ (Jaquetteet. al.,1994. 2). Once the armed conflict is over and peace returns, women's choices, rights, and lives once again tend to become circumscribed by tradition, religion, and male prerogative.There is a vital need for information about what happens to women during and following periods of war—their survival strategies, the metamorphosis of gender relations, the retention of positive changes, the identification of their needs, and the support required to meet those needs (Wallace and March,1991). Attempting to answer such questions, the purpose of this paper is to explore the experiences of Kuwaiti women during and after the Iraqi invasion and occupation of 1990. The authors' contention is that, in terms of gender empowerment, Kuwaiti women's experience during this period was and is no differnt than the experiences of women during and after wartime crises elsewhere. In an attempt to take into account variations of context and historical specificities the impact of Islamic beliefs and practices and their compatibility or incompatibility with women's rights are examined alongside social development/status variables. Copyright © 2001 John Wiley & Sons, Ltd.
Precursor synthesis and radiolabelling of [11C]ADAM: a potential radioligand for the serotonin transporter exploration by PET
Authors: VERCOUILLIE Johnny , TARKIAINEN Jari , HALLDIN Christer , EMOND Patrick , CHALON Sylvie , SANDELL Johan , LANGER Oliver , GUILLOTEAU Denis 
Published: September 2002

AbstractThe serotoninergic system is involved in a variety of neurological and psychiatric disorders. Exploration of the serotonin transporters (5‐HTT) in living human brain by PET would be of great value for better understanding, diagnosis and therapeutic follow up of these diseases. In order to obtain a selective radioligand to explore the 5‐HTT by PET we report the synthesis of [11C]N,N‐dimethyl‐2‐(2‐amino‐4‐iodophenylthio)‐benzylamine ([11C]ADAM). The precursor for labelling N‐demethyl ADAM, was obtained in five steps using 2,5‐dibromonitrobenzene and 2‐thio‐N‐methylbenzamide as starting material. [11C]ADAM was synthesised by N‐alkylation of the precursor using [11C]methyl iodide in DMF. The incorporation yield of [11C]methyl iodide was in the range of 50 to 70%. Finally [11C]ADAM was obtained in 30 minutes synthesis time including HPLC and with a radiochemical purity better than 99%. Copyright © 2001 John Wiley & Sons, Ltd.
Synthesis of fluorine‐18 labeled sulfonureas as β‐cell imaging agents
Authors: Shiue Grace G. , Schirrmacher Ralf , Shiue Chyng‐Yann , Alavi Abass A. 
Published: September 2002

AbstractTolbutamide (1) and glyburide (7) are hypoglycemic drugs used to stimulate insulin secretion in type 2 diabetic patients. We have synthesized their fluorine‐18 labeled analogs, 1‐[(4‐[18F]fluorobenzenesulfonyl)]‐3‐butyl]urea (p‐[18F]fluorotolbutamide, 3a) and N‐{4‐[β‐(2‐[18F]fluoroethoxybenzene carboxamido)ethyl]benzenesulfonyl}‐N′‐cyclohexylurea (2‐[18F]fluoroethoxyglyburide, 6a) as β‐cell imaging agents. Compound 3a was synthesized via two approaches: One‐step synthesis via nucleophilic substitution of p‐nitrotolbutamide (2) with K[18F]/Kryptofix 2.2.2 in either CH3CN or DMSO gave a complicated mixture; a two‐step synthesis via preparation and reaction of 4‐[18F]fluorobenzenesulfonamide with butyl isocyanate in the presence of either copper (I) chloride or borontrifluoride etherate complex in CH3CN followed by HPLC purification yielded compound 3a in an overall yield of 1–2% with a synthesis time of 120 minutes from EOB. Compound 6a was synthesized by alkylation of the corresponding hydroxy precursor (5) with [18F]fluoroethyl tosylate in DMSO at 120°C for 20 minutes followed by HPLC purification in an overall yield of 5–10 % with a synthesis time of 100 minutes from Copyright © 2001 John Wiley & Sons, Ltd.
Highly efficient synthesis of [11C]S12968 and [11C]S12967, for the in vivo imaging of the cardiac calcium channels using PET
Authors: Dolle Frédéric , Valette Héric , Hinnen Françoise , Demphel Stéphane , Bramoulle Yann , Peglion Jean‐Louis , Crouzel Christian 
Published: September 2002

AbstractThe dihydrophyridines S12968 ((−)‐S11568, absolute configuration S) and S12967 ((+)‐S11568, absolute configuration R), 3‐ethyl 5‐methyl (−/+)‐2‐[(2‐(2‐aminoethoxy)ethoxy)methyl]‐4‐(2,3‐dichlorophenyl)‐6‐methyl‐1,4‐dihydropyridine‐3,5‐dicarboxylate, have both an in vitro profile of high potency and of high selectivity for the low‐voltage‐dependent L‐type calcium channel. In this paper, the radiosynthesis of both enantiomers, S12968 and S12967, with carbon‐11, a positron‐emitting isotope (half‐life : 20.4 min) was investigated and oriented towards the preparation of multi milliCuries of radiotracer. Typically, 130–250 mCi (4.81–9.25 GBq) of [11C]S12968 and [11C]S12967 were obtained within 30 min of radiosynthesis (HPLC purification included) with specific radioactivities ranging from 500 to 1000 mCi/μmol (18.5–37.0 GBq/μmol) using no‐carrier‐added [11C]methyl triflate as the alkylating agent and the appropriate, enantiomerically pure carboxylic acid precursor at 100°C for 1 min. Based on preliminary PET experiments, only the levo enantiomer S12968 ((−)‐[11C]‐1) appears to be suitable for myocardial PET imaging as demonstrated in vivo in beagle dogs: with S12968, 85% of the uptake of [11C]S12968 could be inhibited in pretreatment experiments and up to 70% of [11C]S12968 could be displaced. Further investigations are currently underway in order to provide an absolute quantification of ventricular calcium channels with PET. Copyright © 2001 John Wiley & Sons, Ltd.
Labeling of human C‐peptide by conjugation with N‐succinimidyl‐4‐[18F]fluorobenzoate
Authors: Fredriksson Anna , Johnström Peter , Stone‐Elander Sharon , Jonasson Per , Nygren Per‐Åke , Ekberg Karin , Johansson Bo‐Lennart , Wahren John 
Published: September 2002

AbstractWe have labeled proinsulin connecting peptide (C‐peptide) with fluorine‐18 (t½=109.7 min) in order to perform in vivo biodistribution and pharmacokinetic studies with position emission tomography (PET). This study reports the optimization of the conjugation labeling in the N‐terminal with N‐succinimidyl‐4‐[18F]fluorobenzoate ([18F]SFB). In preparative runs N‐4‐[18F]fluorobenzoyl‐C‐peptide ([18F]FB‐C‐peptide) was produced in 8–12% decay‐corrected yields, counted from resolubilized [18F]F−, in less than 5 h. The specific radioactivity of [18F]FB‐C‐peptide, determined using ELISA for one of the preparations, was around 70 GBq/μmol at end of synthesis. Copyright © 2001 John Wiley & Sons, Ltd.
Exchange radioiodination produces inversion at C‐4 of 1‐(4‐deoxy‐4‐iodo‐β‐D‐xylopyranosyl)‐2‐nitroimidazole
Authors: Schneider R.F. , Price W.A. , Chapman J.D. 
Published: September 2002

AbstractThe title compound, 3a, when exchange labeled with 125I results in three new labeled products. The major labeled product (84.1%) is 1‐(4‐deoxy‐4‐iodo‐β‐L‐arabinopyranosyl)‐2‐nitroimidazole, 3b, that could result from inversion of configuration at C‐4. Exchange labeling carried out under conditions of kinetic control yielded dramatically different product ratios than thermodynamic equilibrium reactions. Confirmation of these results was established by extensive 1HNMR spectral analyses. A possible mechanism is presented. Copyright © 2002 John Wiley & Sons, Ltd.
Synthesis of 3‐[[4‐(4‐[18F] fluorophenyl)piperazin‐1‐yl]methyl]‐1H‐pyrrolo[2,3‐b]pyridine
Authors: Eskola Olli , Bergman Jörgen , Lehikoinen Pertti , Haaparanta Merja , Grönroos Tove , Forsback Sarita , Solin Olof 
Published: September 2002

Abstract3‐[[4hyphen;(4‐[18F]fluorophenyl)piperazin‐1‐yl] methyl] ‐1H‐pyrrolo[2,3‐b]pyridine, acandidate to image dopamine D4 receptors, was synthesised via electrophilic fluorination of a trimethylstannyl precursor with high specific radioactivity [18F]F2. The precursor was obtained by a facile four‐step synthetic approach; the trimethylstannyl leaving group was introduced by displacement of iodine utilising palladium catalysis and hexamethyldistannane in an inert solvent. The total radiosynthesis time was 50 min, including purification and formulation for injection. Decay corrected radiochemical yield was <1% as calculated from the amount of [18F]F− produced. Specific radioactivity at the end of synthesis was 12.8–16.4 GBq/μmol. Radiochemical purity was 88–92%. Ex vivo studies in rats showed homogeneous distribution of radioactivity within rat brain. Copyright © 2002 John Wiley & Sons, Ltd.
Magnetic resonance microscopy at 17.6‐Tesla on chicken embryos in vitro
Authors: Hogers Bianca , Gross Dieter , Lehmann Volker , de Groot Huub J.M. , de Roos Albert , Gittenberger‐de Groot Adriana C. , Poelmann Robert E. 
Published: September 2002

AbstractThe non‐destructive nature and the rapid acquisition of a three‐dimensional image makes magnetic resonance microscopy (MRM) very attractive and suitable for functional imaging investigations. We explored the use of an ultra high magnetic field for MRM to increase image quality per image acquisition time. Improved image quality was characterized by a better signal‐to‐noise ratio (SNR), better image contrast, and higher resolution compared to images obtained at lower magnetic field strengths. Fixed chicken embryos at several stages of development were imaged at 7.0‐T (300 MHz) and at 17.6‐T (750 MHz). Maximum intensity projection resulted in three‐dimensional vascular images with ample detail of the embryonic vasculature. We showed that at 750 MHz frequency, an image with approximately three times better SNR can be obtained by T1‐weighting using a standard gadolinium contrast agent, compared to the same measurement at 300 MHz. The image contrast improved by around 20 percent and the contrast‐to‐noise ratio improved by almost a factor of 3.5. Smaller blood vessels of the vascular system were identified at the high field, which indicates a better image resolution. Thus, ultra high field is beneficial for MRM and opens new areas for functional imaging research, in particular when SNR, resolution, and contrast are limited by acquisition time. J. Magn. Reson. Imaging 2001;14:83–86. © 2001 Wiley‐Liss, Inc.