bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dynamic deformation of migratory efferent lymph‐derived cells “trapped” in the inflammatory microcirculation
Authors: Su Mei , West Charles A. , Young Alan J. , He Chufa , Konerding Moritz A. , Mentzer Steven J. 
Published: November 2002

AbstractThe cellular immune response depends on the delivery of lymphocytes from the lymph node to the peripheral site of antigenic challenge. During their passage through the inflammatory microcirculaton, the migratory cells can become transiently immobilized or “trapped” in small caliber vessels. In this report, we used intravital microscopy and temporal area mapping to define the dynamic deformation of efferent lymph‐derived mononuclear cells trapped in the systemic inflammatory microcirculation. Mononuclear cells obtained from the efferent lymph draining the oxazolone‐stimulated microcirculation were labeled with fluorescent dye and reinjected into the feeding arterial circulation. Intravital video microscopy observed thousands of cells passing through the microcirculation; 35 cells were “trapped” in the oxazolone‐stimulated microcirculation. Temporal area maps of the trapped cells demonstrated dramatic slowing and deformation. The cells were trapped in the microcirculation for a median of 8.90 sec (range 5–17 sec) prior to returning to the flow stream. During this period, the cells showed sustained movement associated with both antegrade locomotion (mean cell velocity = 7.92 μm/sec; range 1.16–14.23 μm/sec) and dynamic elongation (median cell length = 73.8 μm; range 58–144 μm). In contrast, efferent lymph‐derived cells passing unimpeded through the microcirculation demonstrated rapid velocity (median velocity = 216 μm/sec) and spherical geometry (median diameter = 14.6 μm). Further, the membrane surface area of the “trapped” cells, calculated based on digital image morphometry and corrosion cast scanning electron microscopy, suggested that the fractional excess membrane of the cells in the efferent lymph was significantly greater than previous estimates of membrane excess. These data indicate that transient immobilization of efferent lymph‐derived mononuclear cells in the systemic inflammatory microcirculation is rare. When “trapping” does occur, the shape changes and sustained cell movement facilitated by excess cell membrane may contribute to the return of the “trapped cells” into the flow stream. © 2002 Wiley‐Liss, Inc.
Rap1 reverses transcriptional repression of TGF‐β type II receptor by a mechanism involving AP‐1 in the human pancreatic cancer cell line, UK Pan‐1
Authors: Fralix Kimberly D. , Zhao Shujie , Venkatasubbarao Kolaparthi , Freeman James W. 
Published: November 2002

AbstractThe TGF‐β signaling pathway has potent anti‐mitogenic effects in epithelial cells and loss of negative growth regulation is often associated with increased tumorigenicity. The human pancreatic ductal adenocarcinoma cell line, UK Pan‐1, which expresses DPC4, is not highly responsive to TGF‐β due to transcriptional repression of TGF‐β type II receptor (RII). Here, we show that UK Pan‐1 cells transfected with a plasmid to overexpress rap1 protein (UK/rap1) causes an increase in RII transcription and restores sensitivity to TGF‐β growth inhibition. The overexpression of rap1 was associated with diminished ras signaling as measured by ras binding domain (RBD)‐binding assays. Electrophoretic mobility shift assays (EMSA) analysis revealed increased binding of nuclear proteins to a previously identified positive regulatory element (PRE1) of the RII promoter in rap1 transfected cells. Competition with an oligo containing the AP‐1 consensus site was able to inhibit this binding of nuclear proteins to the PRE1 region. Further EMSA analysis using antibodies to various AP‐1 components revealed that junB antibodies partially depleted the increase in binding to the PRE1 seen in UK/rap1 cells while antibodies to other AP‐1 constituents such as c‐jun, c‐fos, and ATF‐1 had no effect on binding. Consistent with this data, transient transfection of UK Pan‐1 cells with junB resulted in greater RII transcription (twofold) as measured by RII‐luciferase assay. Mutation of the AP‐1 site inhibited junB‐mediated or rap1‐mediated increases in RII promoter activity. These data suggest that rap1 signaling may mediate an increase in RII transcription via increased binding of nuclear factors including junB to the PRE1 region of the RII promoter. © 2002 Wiley‐Liss, Inc.
Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR‐TKIs): Simple drugs with a complex mechanism of action?
Authors: Normanno Nicola , Maiello Monica R. , De Luca Antonella 
Published: November 2002

AbstractA range of target‐based agents for the treatment of solid tumors are in development. The epidermal growth factor receptor (EGFR) has been identified as a relevant target as it is involved in regulating several cellular functions important in the proliferation and survival of cancer cells, is commonly expressed at high levels in a range of tumors, and high expression is often related to poor prognosis. EGFR is a member of the ErbB family of receptors which also includes ErbB‐2, ErbB‐3, and ErbB‐4. These receptors form dimers of the same type (homodimers) or with other family members (heterodimers), each combination resulting in different downstream effects. Some of the most advanced targeted agents in development are the EGFR tyrosine kinase inhibitors (EGFR‐TKIs), of which ZD1839 (‘Iressa’) is an example. In Phase II monotherapy trials, oral ZD1839 was well tolerated and demonstrated clinically meaningful antitumor activity and symptom relief in pretreated patients with advanced NSCLC. Preclinical studies have suggested that the antitumor activity of ZD1839 does not depend on the level of EGFR expression. Furthermore, in addition to an effect on EGFR signaling, treatment with ZD1839 as well as with other quinazoline EGFR‐TKIs, may also affect signaling of other ErbB family members. EGFR‐TKIs have been shown in preclinical studies to increase the efficacy of cytotoxic drugs and Phase III trials of such combinations are ongoing. On the basis that different signal transduction pathways contribute to the control of tumor growth, future therapeutic approaches are likely to involve combination of different targeted agents. © 2002 Wiley‐Liss, Inc.
Improved design and optimization models for the fixed bed adsorption of acid dye and zinc ions from effluents
Authors: Ko Danny C K , Lee Vinci K C , Porter John F , McKay Gordon 
Published: December 2002

AbstractThe bed depth service time (BDST) design model, which accounts for the change of bed adsorption capacity with service time, has been modified to expand its application and overcome the limiting assumptions of the original BDST analysis. Column experiments were undertaken to test the new model for two adsorption systems, namely zinc ion–bone char and Acid Blue 80 dye‐activated carbon. It was found that the percentage of saturation capacity could be correlated using a square‐root dependence on the service time and this correlation was incorporated into the original BDST analysis to replace the total sorption capacity term, giving the model a much wider application to real systems. The empty bed residence time optimization approach was modified using the same time‐dependent capacity expression and was successfully applied to the metal ion–bone char and the dye‐activated carbon system with the use of equilibrium saturated bed capacity. These modifications to the BDST design model and the EBRT optimization model will give more accurate scale‐up data for the design of large‐scale column adsorption systems.© 2002 Society of Chemical Industry
Critical evaluation of the chemical standardization procedure for measuring gastric emptying of solids
Authors: Goethals P. , Volkaert A. , Van Vlem B. , Vanholder R. 
Published: November 2002

AbstractThe purpose of this study was to evaluate the baking process of yolk spiked with octanoate to measure gastric emptying rate of solids. [1‐11C]octanoate was produced by the reaction of [11C]CO2 with heptyl magnesium bromide in tetrahydrofuran (THF), followed by purification with HPLC. The decay corrected radiochemical yield ranged from 24 to 38% (5.9–9.8 GBq EOS, synthesis time: 25 min; specific radioactivity ∼90 GBq μmol−1). To check the evaporation of [1‐11C]octanoate during the baking process of yolk, [1‐11C]octanoate or potassium [1‐11C]octanoate, respectively, was added. An important fraction of the acid evaporated while for the potassium [1‐11C]octanoate <10% disappeared. Conclusion: potassium (1‐13C)octanoate is a better tracer than (1‐13C) octanoate to study gastroenterological phenomena. Copyright © 2002 John Wiley & Sons, Ltd.
Synthesis of 32P‐labeled intermediates on the purine biosynthetic pathway
Authors: Mehl Ryan A. , Begley Tadhg P. 
Published: November 2002

AbstractA fast and efficient route to 32P‐labeled intermediates on the purine biosynthetic pathway is described. Adenosine kinase catalyzes the phosphorylation of 5‐aminoimidazole‐4‐carboxamide ribonucleoside (AICARs) to give [32P]‐5‐aminoimidazole‐4‐carboxamide ribonucleotide (AICAR). This was then hydrolyzed to [32P]‐4‐carboxy‐5‐aminoimidazole ribonucleotide (CAIR). Treatment of CAIR with N5‐CAIR mutase gave [32P]‐5‐aminoimidazole ribonucleotide (AIR) in milligram quantities. Copyright © 2002 John Wiley & Sons, Ltd.
Ortho‐[18F]Fluoronitrobenzenes by no‐carrier‐added nucleophilic aromatic substitution with K[18F]F–K222—A comparative study
Authors: Karramkam M. , Hinnen F. , Bramoullé Y. , Jubeau S. , Dollé F. 
Published: November 2002

AbstractThe scope of the nucleophilic aromatic ortho‐fluorinations from the corresponding ortho‐halonitrobenzene precursors (halo‐to‐fluoro substitutions) with no‐carrier‐added [18F]fluoride ion as its activated K[18F]F–K222 complex has been evaluated via the radiosynthesis of ortho‐[18F]fluoronitrobenzene, chosen as a model reaction. The parameters studied include the influence of the leaving group in the ortho position of the phenyl ring (–Cl, –Br, –l), the quantity of precursor used, the type of activation (conventional heating or microwave irradiations), the solvent, the temperature and the reaction time. The iodo‐precursor was completely unreactive and the bromo‐precursor gave only low incorporation (<10%) in the optimal conditions used (conventional heating at 145°C or microwave activation, 100 W for 120 s). Only the chloro‐precursor was found reactive in the conditions described above and up to 70% yield was observed for the formation of ortho‐[18F]fluoronitrobenzene ([18F]‐1). In all the experiments, the unwanted ortho‐[18F]fluoro‐halobenzenes, potentially resulting from the nitro‐to‐fluoro substitution, could not be detected. These results will be applied for the radiosynthesis of 5‐[18F]fluoro‐6‐nitroquipazine, a potent radioligand for the imaging of the serotonin transporter with PET. Copyright © 2002 John Wiley & Sons, Ltd.
Synthesis of [14C]‐labelled repinotan hydrochloride and its major metabolite M‐6
Authors: Seidel D. , Conrad M. , Schoof Y. , Schohe‐Loop R. 
Published: November 2002

AbstractFor studies of pharmacokinetics and drug metabolism of the new 5‐HT1A agonist repinotan, the 14C‐labelled version was synthesized. Starting from [U‐14C]phenol, a 10‐step synthesis led to 457 mg (1.58 GBq) of [U‐14C]repinotan hydrochloride, labelled uniformly in the aromatic ring of the chromane moiety. For a study in man, a mono‐carbon‐14 labelled substance was required. Therefore a 7‐step synthesis was performed starting from [carbonyl‐14C]2‐hydroxy‐acetophenone. The yield was 106 mg (0.396 GBq) of [4‐chromane‐14C]repinotan hydrochloride. The carbon‐14 labelled major metabolite, hydroxylated in the 6‐position of the chromane moiety, was synthesised as reference compound. Copyright © 2002 John Wiley & Sons, Ltd.
Synthesis of (±) [5‐3H] N′‐nitrosoanatabine, a tobacco‐specific nitrosamine
Authors: Desai Dhimant , Lin Guoying , Morimoto Hiromi , Williams Philip G. , Bayoumy Karam El‐ , Amin Shantu 
Published: November 2002

AbstractTobacco‐specific N′‐nitrosamines (TSNA) are a unique class of systemic organ‐specific carcinogens. The TSNA are formed by N‐nitrosation of nicotine and of the minor tobacco alkaloids after harvesting of tobacco and during smoking. The N‐nitrosation of anatabine leads to N′‐nitrosoanatabine (NAT; 1‐nitroso‐1,2,3,4‐tetrahydro‐2,3'‐bipyridyl) which requires in‐depth assays in laboratory animals other than the rat. Furthermore, delineation of its tissue distribution and metabolism is needed for structure:activity comparisons with other TSNA and for the assessment of potential human risk from this TSNA. We have, therefore, synthesized (±)[5‐3H]NAT. 5‐Bromo‐3‐pyridine‐carboxaldehyde was condensed with ethyl carbamate prior to Diels–Alder reaction with 1,4‐butadiene to give the racemic anatabine ring system. Hydrolysis, followed by reduction with LiAlT4 and nitrosation, led to (±)[5‐3H]NAT (60% yield, specific activity 266 mCi/mmol, radiochemical purity of >99%). Copyright © 2002 John Wiley & Sons, Ltd.
Synthesis of 14C‐labeled 4‐hydroxyindole as an intermediate for the preparation of (S)‐2‐[4‐[2‐[3‐(indol‐2‐[14C]‐4‐yloxy)‐2‐hydroxypropylamino]‐2‐methylpropyl]‐phenoxy]pyridine‐5‐carboxamide (LY368842‐[indole‐14C]) glycolate
Authors: Czeskis Boris A. , Clodfelter Dean K. , Wheeler William J. 
Published: November 2002

AbstractSynthesis of 4‐hydroxyindole labeled with 14C at the 2‐position was accomplished based on the vicarious nucleophilic substitution reaction of benzyl‐protected 3‐nitrophenol with p‐chlorophenoxyacetonitrile‐[1‐14C]. This was followed by the reductive cyclization of o‐nitrocyanomethyl derivative by palladium catalyzed hydrogenation. p‐Chlorophenoxyacetonitrile‐[1‐14C] was prepared from commercially available p‐chlorophenoxymethyl chloride and sodium cyanide‐[14C]. 4‐Hydroxyindole‐[2‐14C] was used for the synthesis of 14C‐labeled β3 adrenergic agonist LY368842. Copyright © 2002 John Wiley & Sons, Ltd.
Synthesis of [2H3]‐dextromethorphan and its major urinary metabolites [2H3]‐dextrorphan and [2H3]‐dextrorphan‐β‐glucuronide
Authors: Heinkele Georg , Schänzle Gerhard , Mürdter Thomas E. 
Published: November 2002

AbstractStarting from dextromethorphan, [2H3]‐dextrorphan‐β‐glucuronide was synthesized in four steps with [2H3]‐dextromethorphan and [2H3]‐dextrorphan as intermediates with an overall yield of 11%. Copyright © 2002 John Wiley & Sons, Ltd.
10th Conference of the Central European Division e.V. of the International Isotope Society
Authors: Jones J R , Lu S‐Y , Shevchenko V. P. , Nagaev I. Yu. , Myasoedov N. F. , Susan A. B. , Anderskerskevitz R. , Birke F. W. , Switek K‐H. , Wiegerinck Peter , Post Olaf , Hofstede Leontine , van den Heuvel Marcel , Pleiss U. , Seidel D. , Switek K.‐H. , Braunger H. , Seidel Dietrich , Schlecker Rainer , Moenius Thomas , Seiler Max‐Peter , Nozulak Joachim , Burtscher Paul , Almi Mario , Guelfi Simone , Navacchia Maria Luisa , Felicini C. , Giribone D. , Pignatti A. , Fontana E. , Pignatti A. , Fontana E. , McGrath J. W. , Peric Simov B. , Preusser W. , Quinn J. P. , Schmidt S. , Woschek A. , Wuggenig F. , Hammerschmidt F. , Spies H. , Maas Jochen , Krone Volker , Diehl Frank , Coy Johannes , Hoheisel Jörg , Doeberitz Magnus von Knebel , Nees Matthias , Klett Alfred 
Published: November 2002

AbstractUse of Microwaves in Organic Synthesis: Application in the Synthesis of Isotopically Labelled CompoundsPreparation of Tritium‐Labelled BIIL 260 with High Specific RadioactivitySynthesis of [3H]‐, [14C]‐ and [13C,2H]‐labelled Org 12962 DerivativesLabeling of BAY 58‐2667, an Activator of sGCPreparation and Use of [14C]N,N′‐Carbonylditriazole in the Labelling of Urea DerivativesEfficient Carbon‐14 Labeling of 2‐(3‐Hydroxypropyl)‐1H‐benzimidazoleSynthesis of Some 14C‐Labelled FungicidesC‐14 Labelling of NVP‐ABE651 and NVP‐ABE697Synthesis of Carbon‐13,14 Isotopomers of a Novel 4‐Substituted‐2‐Carboxy Tetrahydroquinoline[14C]CH2N2: A Suitable Precursor for the Preparation of 14C‐Labelled AnthracyclinesPreparative HPLC: a Useful Approach to Speed‐up the Purification of Labelled Compounds.Use of Stable Isotopes for the Biosynthesis and Biodegradation of FosfomycinMetalloradiopharmaceuticals for Nuclear MedicineStrategic outlook: Future Methods in DMPK and subsequent requirements for isotopically labelled compoundsIsotopic Imaging of Glass‐based cDNA Microarray HybridizationNew Developments in Radiation Measuring Technique
Congener‐specific determination of dioxins and related compounds by gas chromatography coupled to LRMS, HRMS, MS/MS and TOFMS
Authors: Eljarrat E. , Barceló D. 
Published: November 2002

AbstractTheir characteristics as persistent organic pollutant and their toxicity (2,3,7,8‐TCDD is named as a known human carcinogen) make the dioxins and related compounds a focus of interest in environmental analytical chemistry. In view of the widespread distribution of dioxins in the environment, these compounds must be monitored in several matrices, such as air, effluents, soil, sludge and biological samples. The analytical methodologies are especially difficult owing to the complexity of the mixtures of congeners (210 PCDD/Fs and 209 PCBs) and to the low detection limits required (ppb to ppq). Moreover, time‐consuming sample preparation steps are needed owing to the presence of a large number of interfering compounds. The different toxicity of each congener requires the development of congener specific methods. This review of trace dioxin determination by mass spectrometry (MS) includes sample preparation and chromatographic separation. In this Special Feature, the use of different MS techniques such as low‐resolution MS (LRMS) and high‐resolution MS (HRMS) is discussed in terms of selectivity and sensitivity. The performances of other MS techniques, such as tandem MS (MS/MS) and time‐of‐flight MS (ToFMS), are compared. Quantification techniques, especially the isotopic dilution method, are also discussed. Conclusions and future perspectives are outlined. Copyright © 2002 John Wiley & Sons, Ltd.
Ionization energy reductions in small 2,5‐dihydroxybenzoic acid–proline clusters
Authors: Kinsel Gary R. , Knochenmuss Richard , Setz Patrick , Land C. Mark , Goh Sor‐Koon , Archibong Edet F. , Hardesty Jon H. , Marynick Dennis S. 
Published: November 2002

AbstractThe photoionization of (pro)nDHB (pro = proline, DHB = 2,5‐dihydroxybenzoic acid, n = 0, 1, 2 or 4) clusters was studied both experimentally and computationally. Experimentally the (pro)nDHB clusters are generated in the gas phase by laser desorption and supersonic jet entrainment. The photoionization thresholds are then determined by the mass‐selective measurement of both one‐ and two‐color photoionization efficiency curves. These experiments demonstrate that the ionization energies (IEs) of the (pro)nDHB clusters are substantially reduced in comparison with the IE of free DHB. Computational studies of the (pro)nDHB clusters provide insights into the mechanism of IE reduction. For the (pro)DHB system the IE reduction results from spin delocalization in the ion state of the cluster. In contrast, for the (pro)2DHB and (pro)4DHB clusters the IE reduction results from an inductive delocalization of electron density from pro to DHB in the ground state of the cluster. This latter effect, which is a result of the specific hydrogen‐bonding interactions occurring in the mixed clusters, leads to IE reductions of >1 eV. Finally, determination of the energetics of the (pro)2DHB radical cation demonstrate that the DHB‐to‐proline proton transfer reaction is a barrierless, exoergic process in the ion state and that energetic demands for cluster dissociation to protonated (pro)2 plus a deprotonated DHB radical are substantially lower than those for cluster dissociation to (pro)2 plus DHB+ ·. Cumulatively, these studies provide new energetic and mechanistic insights into both primary and secondary MALDI ionization processes. Copyright © 2002 John Wiley & Sons, Ltd.
Ionization energies of multiply protonated polypeptides obtained by tandem ionization in Fourier transform mass spectrometers
Authors: Budnik Bogdan A. , Tsybin Youri O. , Håkansson Per , Zubarev Roman A. 
Published: November 2002

AbstractIonization energies (IE) of [M + zH]z+ (z+) electrospray‐produced polypeptides were determined by electron ionization in a Penning cell of 4.7 and 9.4 T Fourier transform mass spectrometers. For z = 1+ and substance P, the found IE value of 11.0 ± 0.4 eV is in agreement with that obtained earlier for ions generated with matrix‐assisted laser desorption/ionization. For higher z, the following values were found: 11.7 ± 0.3 eV for 2+ of [Arg‐8]‐vasopressin, 11.1 ± 0.6 eV for 2+ of substance P, 12.2 ± 0.7 eV for 2+ of renin substrate, 13.3 ± 0.4 eV for 3+ of B‐chain of insulin and 14.6 ± 0.6 eV for 4+ and 15.1 ± 0.4 eV for 5+ of melittin. It was found that 90% of existing IE data on polypeptides in the 1.0–3.5 kDa mass range are described with ≤0.5 eV uncertainty by the empirical equation IE(z) = 9.8 + 1.1z. The average IE increase of 1.1 eV/charge is attributed to Coulombic repulsion. The deduced ionization energy of a neutral polypeptide molecule, 9.8 ± 0.3 eV, is consistent with literature expectations. Copyright © 2002 John Wiley & Sons, Ltd.
Electron ionization‐induced fragmentation of R2N2Fe2(CO)6 complexes with distinct geometries of the tetrahedral core: investigation of µ‐1,2‐(1,2‐diaza‐3‐methylcyclopentane)diylbis(tricarbonyliron) and bis(µ2‐acetophenoniminato)bis(tricarbonyliron)
Authors: Zimniak Andrzej 
Published: November 2002

AbstractTwo binuclear bis(tricarbonyliron) title complexes with N2Fe2 tetrahedral cores, 1 and 2, respectively, which show different molecular folding resulting from the appearance (in 1), and absence (in 2) of the NN σ‐bond, were compared in terms of mass spectral fragmentation routes. A multipath fragmentation noted for the molecule 1 revealing internal stress contrasts with the single‐route fragmentation of 2. The fragmentation paths resulting from the admixtures were defined and analyzed from the fragment ion B/E and parent ion B2/E linked scan spectra. Copyright © 2002 John Wiley & Sons, Ltd.
Simultaneous determination of metabolites of trimethylbenzenes, dimethylbenzylmercapturicacid and dimethylhippuric acid, in human urine by solid‐phase extraction followed by liquid chromatography tandem mass spectrometry
Authors: Moriwaki Hiroshi , Watanabe Ayumi , Arakawa Ryuichi , Tsujimoto Yuji , Shimizu Mitsuru , Noda Tsutomu , Warashina Munehiro , Tanaka Masanobu 
Published: November 2002

AbstractWe describe a novel method for the determination of three kinds of dimethylbenzylmercapturic acids (DMM) and six kinds of dimethylhippuric acids (DMH), found in urine as metabolites of trimethylbenzenes, based on liquid chromatography/electrospray ionization tandem mass spectrometry. A solid‐phase extraction procedure was used for the extractions of DMM and DMH from a urine sample, and the separation was performed on a reversed–phase C30 column. The analytes were ionized by electrospray in the positive‐ion mode. Operating in the multiple reaction monitoring mode, the linearity of the relative mass spectrometric responses to the internal standard versus analyte concentrations were established in the range 0.1–100 ng ml−1. The extraction procedure was rapid and the relative standard deviations were below 5%. The detection limits of DMM and DMH in the urine by the proposed method were in the ranges 0.26–0.41 and 0.42–2.0 ng l−1, respectively. Furthermore, DMM and DMH were detected in a urine sample from an individual who did not suffer from occupational exposure to trimethylbenzenes, by using this method. Copyright © 2002 John Wiley & Sons, Ltd.