bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ethical issues in biotechnologies and international trade
Authors: Hulse Joseph H 
Published: January 2005

AbstractNatural and physical sciences are based on determinable facts. What is ethical, as distinct from illegal, is largely a matter of opinion. Scientific and industrial activities related to ancient and modern biotechnologies are among the most critically scrutinised for ethical probity by social activists and journalists. The practices and products of biotechnologies should be judged both deontologically – by motivation and intention, and teleologically – by determinable consequence. Bioethical criteria have been proposed by governments, medical practitioners and philosophers for many centuries. During the past decade, various scientifically competent organisations, national and international, have formulated comprehensive protocols by which to determine effectiveness and safety of novel foods, pharmaceuticals and other biologicals, including those derived from genetically modified organisms. Means and opportunities by which to satisfy the health and nutritional needs of impoverished nations and communities differ significantly from those who enjoy greater affluence. It is distinctly unethical for Europeans and North Americans, whose food and health securities are not at risk, to impose their ethical predilections on poorer nations. Equally reprehensible are the diverse tariff and non‐tariff barriers to equitable international trade, and acts of biopiracy inflicted upon poorer nations. As a wise Asian sage has observed, the planet's resources and scientific ingenuity are sufficient to satisfy everyone's need, but not everyone's greed. Present and predictable world‐wide demand for bioscientists and bioengineers exceeds best estimates of supply. Systematically planned, long‐term investments by governments and bioindustries to generate adequate qualified men and women are urgently needed.© 2002 Society of Chemical Industry.
Single‐step, multiple retroviral transduction of human T cells
Authors: Abad José Luis , Serrano Fernando , Román Ascensión L. San , Delgado Rafael , Bernad Antonio , González Manuel A. 
Published: January 2005

AbstractBackgroundRetroviral transduction of human peripheral blood T cells has considerable potential in the development of gene therapy strategies for immunological disorders. New vectors and experimental procedures have been developed for efficient transduction of several genes into human T cells.MethodsBicistronic retroviral vectors encoding distinct cell markers were used for the simultaneous multiple transduction of a human T‐cell line (MT‐2), as well as of human peripheral blood T cells from normal donors. Transduction efficiencies were evaluated by flow cytometry and double‐ and triple‐transduced cells were isolated by fluorescence cell sorting.ResultsFour new bicistronic retroviral vectors were developed that express different gene markers under the control of the internal ribosome entry site (IRES) of the encephalomyocarditis virus. These markers are, respectively, enhanced green fluorescent protein (EGFP), β‐galactosidase, and truncated versions of human nerve growth factor receptor (ΔNGFR) and human growth hormone receptor (ΔGHR). A single 1 h spinoculation infection, performed in the presence of polybrene and using transiently produced amphotropic retroviral particles, was sufficient to obtain transduction efficiencies consistently greater than 50% on human peripheral blood T lymphocytes which had been previously stimulated for 3 days with immobilized anti‐CD3. The transient production of viral particles encoding EGFP, ΔNGFR, and ΔGHR markers in the same viral supernatant has allowed up to three different genes to be introduced simultaneously into human T cells.ConclusionsThis study describes new experimental conditions for efficient single‐step multiple transduction of human primary T lymphocytes. The procedure could be of interest for the development of gene therapy approaches. Copyright © 2002 John Wiley & Sons, Ltd.
Encapsulated cells producing retroviral vectors for in vivo gene transfer
Authors: Saller Robert M. , Indraccolo Stefano , Coppola Vincenzo , Esposito Giovanni , Stange Jan , Mitzner Steffen , Amadori Alberto , Salmons Brian , Günzburg Walter H. 
Published: January 2005

AbstractBackgroundBecause gene therapy of the future will primarily take an in vivo approach, a number of problems associated with its current implementation exist. Currently, repeated delivery of a vector in vivo is necessary to ensure adequate transfer of the therapeutic gene. This may lead to the development of an immune response against the vector, thus interfering with gene delivery. To circumvent this problem, retroviral vector packaging cells that permanently produce recombinant retroviral vector particles have been encapsulated.MethodsVector (pBAG)‐producing amphotropic cells were encapsulated in beads composed of polymerized cellulose sulphate. These capsules were analysed in vitro for expression of the vector construct using X‐gal staining, as well as for the release of particles by performing RT‐PCR from culture supernatant. Infectivity studies were performed in vitro and in vivo. The latter was assayed using histological sections of the microcapsule and the surrounding area stained for β‐galactosidase activity and by RT‐PCR.ResultsIn culture, the virus‐producing cells inside the capsules remained viable and released virus into the culture medium for at least 6 weeks. To test whether these capsules, upon implantation into mice, also release vector virions that infect the surrounding cells, two different models were used. In the first, capsules were implanted in the fat pad of the mammary gland of Balb/c mice. The capsules were well tolerated for at least 6 weeks and a self‐limiting inflammatory reaction without any other gross immune response was observed during this period. Furthermore, the virus‐producing cells remained viable. In the second model, SCID mice were immunologically reconstituted by subcutaneous implantation of thymus lobes from MHC‐identical Balb/c newborn mice and gene transfer into lymphoid cells was achieved by retroviral vectors released by co‐implanted capsules.ConclusionThe implantation of such capsules containing cells that continually produce retroviral vector particles may be of use for in vivo gene therapy strategies. The data presented demonstrate the feasibility of the concept. Copyright © 2002 John Wiley & Sons, Ltd.
Coping with, and cashing in on, international capital volatility
Authors: Bird Graham , Rajan Ramkishen S. 
Published: January 2005

AbstractThe political economy of currency taxation suggests that the idea will receive more support if it can be shown to make a significant contribution to offsetting the perceived inefficiencies of private international capital markets. This paper explores what can be expected from a currency tax in this respect. It shows that there are simple but neglected analytical issues that make such a tax an attractive idea. If the tax is relatively ineffective in helping to avoid financial crises and calming markets, it will be relatively effective at providing the resources necessary to mitigate the aftermath of such events. The paper offers new proposals for using the revenue from currency taxation to finance the operations of the IMF. © 2001 John Wiley & Sons, Ltd.
Defining the category of ‘small’ states
Authors: Crowards Tom 
Published: January 2005

AbstractThere is no widely accepted definition of a small state. Most previous definitions have been based upon arbitrarily chosen cut‐off values of selected criteria. The present study attempts to categorize the size of 190 states according to population, land area and total income. An initial categorization is based upon observation of each series to identify discontinuities in the distributions. Cluster analysis is then employed to identify groups of countries that share similar size‐related characteristics. A classification based on non‐hierarchical cluster analysis is proposed, generating four clusters from equally spaced initial cluster‐centres. On this basis, 79 countries are classified as ‘small’. The reasons for deviation from recent categorizations of small countries are explored, the primary cause being the inclusion of some countries with very low levels of income. Copyright © 2002 John Wiley & Sons, Ltd.
Innovation in finance and movement to client‐centered credit
Authors: Von Pischke J. D. 
Published: January 2005

AbstractProgression from product‐centred to client‐centered lending is made possible by innovation, which is by definition cost‐reducing. Innovation in finance occurs in three ways: lengthening term structure, reducing transaction costs, and refining valuation processes. Each of these involves risk. The Thesis Statement is consistent with observed market behaviour but may be criticized for insufficient attention to risk as part of the mechanics of the progression it portrays. As is rapidly occurring in the US, personal credit in other countries will move toward being based almost entirely on empirical probability and hence client‐centered as foreseen in the Statement.In the meantime, the market for money progresses at various speeds from being product‐centered to being client‐centered. When this progression is complete, marketing will be as strategically important as risk management. To the extent that marketing is thought, prematurely, to trump risk management as the key to success, and to the extent meeting client ‘needs’ is viewed as the primary objective, attempts at innovation are likely to fail. When this failure occurs, the social and economic benefits of denying loans will be foregone, hindering development. Questionable projects with problematic sponsors and improper financing will be taken on, limiting growth. Copyright © 2002 John Wiley & Sons, Ltd.
Preparation and a simple one‐step purification of [His1‐mono‐125I‐Tyr10,Nle27]‐hGHRH(1‐32)‐NH2
Authors: Gardi Janos , Krueger James M. , Speth Robert C. 
Published: January 2005

AbstractA one‐step purification of [His1‐mono‐125I‐Tyr10,Nle27]‐hGHRH(1‐32)‐NH2, prepared using chloramine‐T, by HPLC with isocratic elution is described. The labeled GHRH analog was suitable for GHRH receptor binding assays. Copyright © 2002 John Wiley & Sons, Ltd.
Tritiation of SR141716 by metallation–iodination–reduction: tritium‐proton nOe study
Authors: Seltzman Herbert H. , Ivy Carroll F. , Burgess Jason P. , Wyrick Christopher D. , Burch David F. 
Published: January 2005

AbstractThe central cannabinoid receptor antagonist SR141716, N‐(piperidin‐1‐yl)‐5‐(4‐chlorophenyl)‐1‐(2, 4‐dichlorophenyl)‐4‐methyl‐1H‐pyrazole‐3‐carboxamide, was synthesized from commercially available starting materials. Condensation of an aryl hydrazine with a diketone followed by base promoted isomerization/cyclization of the intermediate anti‐imine gave the pyrazole acid which was converted to the title hydrazide via its acid chloride. Facile iodination via metallation followed by in situ trapping with an iodine source gave a modest yield of the iodinated SR141716. The iodine was selectively reduced with tritium gas and catalyst while retaining the three aryl chlorine atoms in the structure. The tritiated SR141716 exhibited a tritium‐proton nOe both definitively identifying the position of the tritium as well as the sought isomer of the diarylpyrazole. This work provides a direct method for the preparation of preferred iodinated aryl substrates that offer advantages where selectivity and high incorporation in catalytic reduction is sought. Copyright © 2002 John Wiley & Sons, Ltd.
Synthesis of [11C]atipamezole, a potential PET ligand for the α2‐adrenergic receptor in the brain
Authors: Roeda D. , Sipilä H.T. , Bramoullé Y. , Enas J. D. , Vaufrey F. , Dollé F. , Crouzel C. 
Published: January 2005

AbstractThe α2‐adrenergic receptor antagonist atipamezole has been labelled with carbon‐11 using [11C]formaldehyde and 2‐ethyl‐2‐oxoacetylindane. Various routes are proposed for the synthesis of the latter: oxidation of 2‐acetyl‐2‐ethylindane, hydrolysis of 2‐diethoxy‐2‐indane and oxidation of 2‐diazoacetyl‐2‐ethylindane. The average radiochemical yield of [11C]atipamezole was 24% based on [11C]formaldehyde, and the synthesis time, including HPLC purification and formulation, was 45 min. Copyright © 2002 John Wiley & Sons, Ltd.
Synthesis of deuterated‐BCX‐1777, a potent inhibitor of purine nucleoside phosphorylase
Authors: Kezar Hollis S. , Hutchison Tracy L. , Tyler Peter C. , Morris Philip E. 
Published: January 2005

AbstractBCX‐1777, a novel inhibitor of the enzyme purine nucleoside phosphorylase, mimics the charged ribosyl oxocarbenium ion formed during the transition state of the enzyme‐catalyzed CN bond cleavage of nucleosides. BCX‐1777 is a slow‐onset, tight‐binding inhibitor with a Ki* of 23 pM and is one of the most potent inhibitors known for the enzyme. In support of our BCX‐1777 program, a mass spectrometric assay has been developed utilizing 5′‐[2H]‐BCX‐1777 as an internal standard. The synthesis of 5′‐[2H]‐BCX‐1777 is described in this report. Copyright © 2002 John Wiley & Sons, Ltd.
Synthesis of (±) 3‐(6‐nitro‐2‐quinolinyl)‐[9‐methyl‐11C]‐3,9‐diazabicyclo‐[4.2.1]‐nonane ([11C‐methyl]NS 4194)
Authors: Jensen Svend B. , Bender Dirk , Smith Donald F. , Scheel‐Krüger Jørgen , Nielsen Elsebet Ø. , Olsen Gunnar M. , Peters Dan , Gjedde Albert 
Published: January 2005

Abstract(±) 3‐(6‐Nitro‐2‐quinolinyl)‐[9‐methyl‐11C]‐3,9‐diazabicyclo‐[4.2.1]‐nonane ([11C‐methyl]NS 4194), a selective serotonin reuptake inhibitor (SSRI), was synthesised within 35 min after end of bombardment with a radiochemical purity >98%. It had a decay‐corrected radiochemical yield of 7% after preparative HPLC, and a specific radioactivity around 37 GBq/μmol (EOS). A typical production starting with 40 GBq [11C]CO2 yielded 800 MBq of radiolabelled [11C‐methyl]NS 4194 in a formulated solution. The synthesis of the precursor to [11C‐methyl]NS 4194, (±) 9‐H‐3‐[6‐nitro‐(2‐quinolinyl)]‐3,9‐diazabicyclo‐[4.2.1]‐nonane, as well as the unlabelled analogue (±) 9‐methyl 3‐[6‐nitro‐(2‐quinolinyl)]‐3,9‐diazabicyclo‐[4.2.1]‐nonane (NS 4194), are also described. Copyright © 2002 John Wiley & Sons, Ltd.
Novel synthesis of [1‐11C]γ‐vinyl‐γ‐aminobutyric acid ([1–11C]GVG) for pharmacokinetic studies of addiction treatment
Authors: Zhang Zongren , Ding Yu‐Shin , Studenov Andrei R. , Gerasimov Madina R. , Ferrieri Richard A. 
Published: January 2005

Abstractγ‐Vinyl‐γ‐aminobutyric acid (GVG, Vigabatrin®), a suicide inhibitor of GABA‐transaminase (GABA‐T), has been suggested as a new drug for the treatment of substance abuse. In order to better understand its pharmacokinetics and potential side effects, we have developed a radiosynthesis of carbon‐11 (t1/2=20 min) labeled GVG for positron emission tomographic (PET) studies. We report here a novel synthetic strategy to prepare the precursor and to efficiently label GVG with C‐11. 5‐Bromo‐3‐(carbobenzyloxy)amino‐1‐pentene was synthesized in five steps from homoserine lactone, including reduction and methylenation. This was used in a one‐pot, two‐step radiosynthesis. Displacement of bromide with no‐carrier‐added [11C]cyanide followed by acid hydrolysis afforded [1‐11C]GVG with decay corrected radiochemical yields of 27±9% (n=6, not optimized) with respect to [11C]cyanide in a synthesis time of 45 min. Copyright © 2002 John Wiley & Sons, Ltd.
Preparation of N′4‐[11C]methyl‐ciprofloxacin for positron emission tomography studies
Authors: Goethals Patrick , Volkaert Anneke 
Published: January 2005

AbstractThe synthesis of N′4‐[11C]methyl‐ciprofloxacin for pharmacological studies using positron emission tomography is described. The starting material was treated with [11C]methyl iodide at 120°C in DMF for 5 min. After HPLC separation on a C18‐column with water/ethanol as mobile phase, the [11C]methyl labelled compound was produced with a radiochemical yield of at least 25% (end of synthesis from [11C]CO2). Activities from 1.48 to 2.22 GBq (40 to 60 mCi) were obtained 1 h after the irradiation, ready for intravenous injection. The carrier ranged between 0.05 and 0.08 μmol (0.010–0.016 μmol/ml). Copyright © 2002 John Wiley & Sons, Ltd.
11C labelling of AG957—a potential tyrphostin radiotracer for PET
Authors: Ackermann Uwe , Tochon‐Danguy Henri J. , Young Kenneth , Sachinidis John I. , Gordon Chan J. , Scott Andrew M. 
Published: January 2005

AbstractCarbon‐11 labelled 4‐(N‐2,5‐dihydroxybenzyl)amino methyl benzoate (AG957), a potential radiotracer for imaging bcr–abl receptors was synthesized. [11C]AG957 was prepared by labelling 4‐aminobenzoic acid using [11C]CH3I, which affords the corresponding [11C] methyl ester in excellent yields. Subsequent condensation of the amino group with 2,5‐dihydroxy‐benzaldehyde formed the respective Schiff base. Reduction of this compound with NaBH3CN gave [11C]AG957 in overall decay corrected radiochemical yield of 65–75% (based on 11CH3I) with an average specific radioactivity of 40 GBq/μmol (1.1 Ci/μmol). The total synthesis time from EOB including formulation was 45 min. At physiological pH, the compound was found to be sufficiently stable for in vitro and in vivo investigations. Copyright © 2002 John Wiley & Sons, Ltd.
C‐Terminal 18F‐fluoroethylamidation exemplified on [Gly‐OH9] oxytocin
Authors: Jelinski M. , Hamacher K. , Coenen H. H. 
Published: January 2005

AbstractThe no‐carrier‐added (n.c.a.) 18F‐fluoroethylamidation of the acid function of the protected nonapeptide Boc–Cys–Tyr(tBu)–Ile–Gln(Mtt)–Asn(Mtt)–Cys–Pro–Leu–Gly–OH forming the labelled peptide hormone derivative [Gly‐(2‐[18F]fluoroethyl)NH9]‐oxytocin is described. The labelling conditions were elaborated using a protected tripeptide, identical to the C‐terminal sequence of oxytocin. The prosthetic group n.c.a. 2‐[18F]fluoroethylamine was synthesised via cryptate mediated n.c.a. 18F‐fluorination of N‐Boc‐2‐(p‐toluenesulfonyloxy)ethylamine in DMSO (RCY: ca. 60%) and subsequent deprotection with a radiochemical yield of 46±5%. [18F]Fluoroethylamine was reacted with Z–Pro–Leu–Gly–OH in presence of the coupling reagent TBTU or with activated esters of the model‐tripeptide. The activated ester method as well as the condensation in presence of TBTU yielded ⩾90% of the 18F‐fluoroethyl‐amidated tripeptide. TBTU‐mediated condensation of n.c.a. 2‐[18F]fluoro‐ethylamine with the C‐terminal free acid group of protected oxytocin gave the radiochemical yield of about 75%. Deprotection under acidic conditions led to the formation of [Gly–(2‐[18F]fluoroethyl)NH9]oxytocin within 75 min with a radiochemical yield of about 30% as measured by analytical HPLC. Copyright © 2002 John Wiley & Sons, Ltd.
Solid phase preparations of 99mTc labeled radiopharmaceuticals
Authors: Rao Ponugoti S. , Li Hongyu , Reddy Kishan C. , Thakur Mathew L. 
Published: January 2005

AbstractFor the preparation of most 99mTc radiopharmaceuticals, SnCl2 has remained the agent of choice for reduction of Tc7+ to lower valency states, which facilitates its chelation by compounds of diagnostic importance. We have developed a simple technique in which SnCl2 lyophilized in a glass vial, either alone or on a solid matrix of polymeric microspheres (beads), was used. Tin‐113 (t1/2 – 115 d) was used as a tracer, which facilitated quantitative assessment of loss or release of tin in the reaction mixtures. The feasibility and efficacy of this technique were examined for preparations of four 99mTc‐ labeled peptides, in which SnCl2 was used as a reducing agent for radiolabeling, a procedure well established in our laboratory. Labeling efficiencies for all four peptides using SnCl2 on solid phase was greater than 95%, as compared to less than 90% (P=0.05) for SnCl2 lyophilized without the solid matrix. Colloid formation was less than 3% in either case. The stability of SnCl2 was greater than six months for solid matrix, and less for that without the microspheres. The 113Sn measured as a daughter product 113mIn indicated that release of SnCl2 from microspheres in reaction mixture was 85±3%, as compared to 80±5% lyophilized alone. The recovery of 99mTc in solution from microspheres was 95–100%. The large size of the microspheres used (649 μm) eliminated the risk of drawing them through a needle in a syringe used for injection of a preparation. Copyright © 2002 John Wiley & Sons, Ltd.
Specific labelling of nucleosides and nucleotides with 13C and 15N
Authors: Milecki Jan 
Published: January 2005

AbstractSynthetic methods leading to nucleosides and deoxynucleosides specifically labelled with 13C and 15N are reviewed. The paper covers labelling the sugar part of the molecule (with 13C) and the aglycone part (both with 13C and 15N). Synthetic methods for labelling at every relevant site of the nucleoside molecule are discussed. The paper also presents the strategies for the synthesis of multilabelled nucleosides. Copyright © 2002 John Wiley & Sons, Ltd.
Synthesis of selectively 15N‐ or 13C‐labelled malachite green
Authors: DeFina Steven C. , Dieckmann Thorsten 
Published: January 2005

AbstractTwo complimentary syntheses of selectively 15N‐ or 13C‐labelled malachite green hydrochloride were developed in order to provide labelled ligands for structural studies of RNA aptamer/ligand complexes. The 15N‐ and 13C‐labelled versions of the dye have been used in NMR studies to probe the changes in the electronic charge distribution and dynamics of the dye upon binding to RNA. Copyright © 2002 John Wiley & Sons, Ltd.
Microbiotic synthesis of 14C‐ringlabelled aminodinitrotoluenes (ADNT) and diaminonitrotoluenes (DANT)
Authors: Kröger Mario , Fels Gregor 
Published: January 2005

AbstractThe four 14C‐ringlabelled TNT‐metabolites 2‐aminodinitrotoluene (2‐ADNT), 4‐aminodinitrotoluene (4‐ADNT), 2,4‐diaminonitrotoluene (2,4‐DANT) and 2,6‐diaminonitrotoluene (2,6‐DANT) were synthesized in one step from TNT by reduction with baker's yeast (Saccharomyces cervisiae). Copyright © 2002 John Wiley & Sons, Ltd.
Synthesis of MMP inhibitor radiotracers [11C]methyl‐CGS 27023A and its analogs, new potential PET breast cancer imaging agents
Authors: Fei Xiangshu , Zheng Qi‐Huang , Hutchins Gary D. , Liu Xuan , Stone K. Lee , Carlson Kathy A. , Mock Bruce H. , Winkle Wendy L. , Glick‐Wilson Barbara E. , Miller Kathy D. , Fife Rose S. , Sledge George W. , Sun Hui Bin , Carr Raymond E. 
Published: January 2005

Abstract[11C]Methyl‐CGS 27023A (1a) and its analogs [11C]methyl‐2‐picolyl‐CGS 27023A (1b), [11C]methyl‐benzyl‐CGS 27023A (1c), [11C]methyl‐2‐nitro‐CGS 27023A (1d), [11C]methyl‐3‐nitro‐CGS 27023A (1e), and [11C]methyl‐4‐nitro‐CGS 27023A (1f), novel radiolabeled matrix metalloproteinase (MMP) inhibitors, have been synthesized for evaluation as new potential positron emission tomography (PET) breast cancer imaging agents. The appropriate precursors for radiolabeling were obtained in four to five steps from starting material amino acid D‐valine with moderate to excellent chemical yields. Precursors were labeled by [11C]methyl triflate through 11C–O‐methylation method at the aminohydroxyl position under basic conditions and isolated by solid‐phase extraction (SPE) purification to produce pure target compounds in 40–60% radiochemical yields (decay corrected to end of bombardment), in 20–25 min synthesis time. Copyright © 2002 John Wiley & Sons, Ltd.
Labelled compounds of interest as antitumour agents – VIII. Synthesis of 2H‐isotopomers of pentamethylmelamine and of a potential prodrug thereof
Authors: Ferrer Sandra , Naughton Declan P. , Threadgill Michael D. 
Published: January 2005

AbstractTreatment of 2‐chloro‐4,6‐(dimethylamino)‐1,3,5‐triazine with trideuteromethylamine gave 4,6‐(dimethylamino)‐2‐trideuteromethyl‐1,3,5‐triazine, an isotopomer of the experimental anticancer agent pentamethylmelamine (PMM). Mitsunobu coupling with 1,2‐dimethyl‐3‐hydroxymethyl‐5‐methoxy‐indole‐4,7‐dione gave 1,2‐dimethyl‐3‐(N‐(4,6‐bis(dimethylamino)‐1,3,5‐triazin‐2‐yl)‐N‐trideuteromethylaminomethyl)‐5‐methoxyindole‐4,7‐dione. This conjugate is a potential reductively triggered prodrug of PMM. Copyright © 2002 John Wiley & Sons, Ltd.