bluuebunny/crossref_metadata_2025_split huggingface dataset:
Synthesis of deuterium‐labelled coenzyme Q10
Authors: Hamamura Kimio , Yamagishi Yoji , Kijima Shizumasa , Suzuki Takeshi , Mori Yutaka , Nakamura Tetsuya 
Published: October 2002

AbstractDeuterium‐labelled coenzyme Q10 ([2‐CD3‐1′‐CD2]coenzyme Q10, coenzyme Q10‐d5 ) was synthesized by condensation of 2,3‐dimethoxy‐[5‐CD3]methyl‐1, 4‐hydroquinone with [1‐CD2]decaprenol. Five positions were selected for deuteration as replacement at these positions allowed examination of every step of the synthesis. This examination was carried out by a combination of 1H‐ and 13C‐nuclear magnetic spectrometry and mass spectrometry. Further, these positions have been proved to be metabolically stable. This reagent makes simultaneous quantification of the source of coenzyme Q10 (exogenously supplied or endogenously supplied) possible in biological samples by measurements on gas chromatography–mass spectrometry. Copyright © 2002 John Wiley & Sons, Ltd.
Synthesis of [3′‐14C] coenzyme Q10
Authors: Hamamura Kimio , Yamatsu Isao , Minami Norio , Yamagishi Yoji , Inai Yuichi , Kijima Shizumasa , Nakamura Tetsuya 
Published: October 2002

AbstractRadio‐labelled coenzyme Q10, labelled at the 3′‐position with 14C, was synthesized starting from natural solanesol and ethyl [3‐14C] acetoacetate. The radiochemical yield was 8.0% from ethyl [3‐14C] acetoacetate. The specific radioactivity of the product was 44.8 μCi, 1.66 MBq/mg. The specific radioactivity and radiochemical purity are sufficiently high to enable us to use this labelled form of coenzyme Q10 in metabolic studies. Copyright © 2002 John Wiley & Sons, Ltd.
Efficient synthesis and formulation of (R)‐(−)‐[11C]Deprenyl, a selective radioligand for the quantification of MAO‐B activity using PET
Authors: Dolle Frédéric , Bramoulle Yann , Hinnen Françoise , Fowler Joanna S. 
Published: October 2002

AbstractCarbon‐11 labeled (R)‐(−)‐Deprenyl is the tracer of reference for the quantification of monoamine oxidase (MAO)‐B activity with PET. In this paper, its radiosynthesis is re‐investigated and oriented towards the preparation of multi‐milliCuries of radiotracer. Typically, using no‐carrier‐added [11C]methyl triflate as the alkylating agent, 140–190 mCi (5.1–7.0 GBq) of (R)‐(−)‐[11C]Deprenyl was obtained within 30 min of radiosynthesis (including HPLC purification and formulation) with specific radioactivities ranging from 0.8 to 1.2 Ci/μmol (29.6–44.4 GBq/μmol). The high efficiency of these radiosyntheses allows for multi‐injection protocols and kinetic approaches for absolute quantification of the tracer. Copyright © 2002 John Wiley & Sons, Ltd.
Synthesis and preliminary PET study of the 5‐HT7 receptor antagonist [11C]DR4446
Authors: Zhang Ming‐Rong , Haradahira Terushi , Maeda Jun , Okauchi Takashi , Kida Takayo , Obayashi Shigeru , Suzuki Kazutoshi , Suhara Tetsuya 
Published: October 2002

AbstractDR4446 (1‐methyl‐2a‐[4‐(4,5,6,7‐tetrahydrothieno[3,2‐c]pyridin‐5‐yl)butyl]‐2a,3,4,5‐tetrahydro‐1H‐benz[cd]indole‐2‐one) is a potent 5‐HT7 receptor antagonist (Ki=9.7 nM) with a high selectivity over other 5‐HT family receptors (Ki for 5‐HT1A: 770 nM; for other 5‐HT receptors: >1000 nM). As a positron emission tomography (PET) tracer for the 5‐HT7 receptor, [11C]DR4446 was synthesized at high radiochemical purity ( >98%) with specific activity of 73–120 GBq/μmol at the end of synthesis by the alkylation of the desmethyl precursor (1) with [11C]CH3I in the presence of NaH. A PET study in monkey demonstrated that [11C]DR4446 had good permeability into the brain, and had a specific binding component in the brain regions including the thalamus, possibly an area in the 5‐HT7 receptors. Metabolite analysis showed that [11C]DR4446 was relatively stable and low percentages of two radio‐labeled metabolites were detected in the plasma of monkey using HPLC. Copyright © 2002 John Wiley & Sons, Ltd.
From chiral bromo[13,14Cn]acetyl sultams to complex molecules singly/multiply labelled with isotopic carbon
Authors: Voges R. 
Published: October 2002

AbstractThe chiral bromo[13,14Cn]acetyl sultams (+)‐ and (−)‐[13,14Cn]BABS 1a, 1b have been demonstrated to be highly efficient, versatile and practical synthons to numerous enantiomerically pure singly and multiply labelled building blocks. The trichlorotitanium enolates derived from 1a, 1b undergo aldol addition reactions with aldehydes providing easily purified, crystalline syn‐2‐bromo‐3‐hydroxy [13,14Cn]carboxylic acid derivatives with excellent diastereo‐selectivity. These can serve as starting materials for e.p. singly/multiply labelled α‐substituted β‐hydroxy acids, β‐substituted/branched α‐hydroxy acids and α‐unsubstituted β‐hydroxy acids. Furthermore, 1a, 1b can be easily converted to the (+)/(−)‐[13,14Cn]DPMGBS 6, (+)/(−)‐[13,14Cn]ITCABS 8 and (+)/(−)‐[13,14Cn]PABS 10 synthons, which significantly enlarges the spectrum of readiliy accessible intermediates. 6 Provides e.p. labelled α‐amino acids, 8 can be employed for the preparation of e.p. labelled α‐amino‐β‐hydroxy acids (threonine type). Synthon 10 reacts with aldehydes to chiral E‐configured enoyl sultams 11 which serve as starting materials for a broad variety of e.p. singly/multiply labelled α,β‐substituted/branched, acyclic and cyclic carboxylic acid derivatives. Finally, aldehydes, generated by reductive cleavage of the auxiliary from the primary α,β‐substituted acyl sultams, react with Ph3P=COOR to give γ,δ‐substituted α,β,‐unsaturated esters, which in turn can be readily converted to highly functionalized e.p. labelled intermediates. This methodology has been extensively exploited for the synthesis of a broad spectrum of carbon‐14 labelled drug substances e.g. Taxol, Valsartan, Everolimus, Lipid X, NVP IMM125, SDZ ISQ844, SDZ PRI05 and the cyclosporin derivatives Valspodar, NVP IMM125, NVP NIM811. Copyright © 2002 John Wiley & Sons, Ltd.
Development of phenotypic differences in sensillum populations on the antennae of a grasshopper, Schistocerca americana
Authors: Chapman R.F. 
Published: October 2002

AbstractThe development of diet‐induced phenotypic differences in numbers of sensilla on the antennae of the grasshopper Schistocerca americana was studied using the exuviae produced at each molt. This made it possible to follow changes within an individual insect. In the first instar, insects had similar numbers of four sensillum types: uniporous trichoid sensilla, coeloconic sensilla, and large and small multiporous basiconic sensilla. Rearing on lettuce resulted in sixth instars with greater numbers of three sensillum types than siblings reared on an artificial diet. The first statistically significant differences between treatments in numbers of trichoid sensilla and large basiconic sensilla occurred in the third and fourth instars, respectively. No major reductions in sensillum numbers occurred at any time and the phenotypic differences resulted from differences in the numbers added at each molt. J. Morphol. 254:186–194, 2002. © 2002 Wiley‐Liss, Inc.
Nuclear medicine applications in molecular imaging
Authors: Blankenberg Francis G. , Strauss H. William 
Published: October 2002

AbstractWith the emergence of the new field of molecular imaging, there is an increasing demand for development of sensitive and safe novel imaging agents that can be rapidly translated from small animal models into patients. Nuclear medicine and positron emission tomography (PET) techniques have the ability to detect and serially monitor a variety of biologic and pathophysiologic processes, usually with tracer quantities of radiolabeled peptides, drugs, and other molecules at doses free of pharmacologic side effects, unlike the current generation of intravenous agents required for magnetic resonance (MR) and computed tomography (CT) scanning. In this article, we will review a representative sampling of the wide array of radiopharmaceuticals developed specifically for nuclear medicine radionuclide imaging that have been approved for clinical use, and those in pre‐clinical trials. We will also review the existing strategies used to select the appropriate biologic markers and targets for radionuclide labeling that have been employed in the development of novel radiotracers and the imaging of small animals with new microSPECT (single photon emission computed tomography) technologies. J. Magn. Reson. Imaging 2002;16:352–361. © 2002 Wiley‐Liss, Inc.
Vascular‐targeted molecular imaging using functionalized polymerized vesicles
Authors: Li King C.P. , Bednarski Mark D. 
Published: October 2002

AbstractIn this review we will discuss the use of multivalent polymerized vesicles (PVs) combined with magnetic resonance imaging (MRI) and gamma scintigraphy to image expression of vascular molecular receptors in vivo. Specifically, we will present our data on the use of this technology to design imaging agents toward specific vascular receptors in both a mouse and rabbit tumor model and in the EAE mouse, a model for human multiple sclerosis (MS). Examples will be shown where the in vivo specificity of the targeted molecular imaging agents was validated in the animal models. Since the PVs are designed to carry either contrast or therapeutic agents or both, we can potentially use vascular‐targeted imaging for selecting patients and guiding vascular‐targeted therapies in these patients. Using this combined vascular‐targeted imaging and therapy approach, personalized treatment can potentially be delivered, maximizing efficacy and minimizing side effects. J. Magn. Reson. Imaging 2002;16:388–393. Published 2002 Wiley‐Liss, Inc.
Derivatization of small biomolecules for optimized matrix‐assisted laser desorption/ionization mass spectrometry
Authors: Tholey Andreas , Wittmann Christoph , Kang Min‐Jung , Bungert Ditte , Hollemeyer Klaus , Heinzle Elmar 
Published: October 2002

AbstractMatrix‐assisted laser desorption/ionization time‐of‐flight mass spectrometry (MALDI‐TOFMS) is a powerful tool for the measurement of low molecular mass compounds of biological interest. The limitations for this method are the volatility of many analytes, possible interference with matrix signals or bad ionization or desorption behavior of the compounds. We investigated the application of well‐known and straightforward one‐pot derivatization procedures to circumvent these problems. The derivatizations tested allow the measurement and the labeling of alcohols, aldehydes and ketones, carboxylic acids, α‐ketocarboxylic acids and amines. Copyright © 2002 John Wiley & Sons, Ltd.
Open‐access liquid chromatography/mass spectrometry in a drug discovery environment
Authors: Mallis Larry M. , Sarkahian Ani B. , Kulishoff John M. , Watts William L. 
Published: October 2002

AbstractThe use of open‐access mass spectrometry to monitor synthetic chemistry reactions, and also the integrity and purity of new chemical entities, has been a part of the medicinal chemist's tool‐box for more than 5 years. Originally in our group at Wyeth Research there were two open‐access methods available to the chemists, flow injection analysis (FIA) and liquid chromatography/mass spectrometry (LC/MS). The FIA method was ∼3 min long, while the LC/MS method was ∼20 min long (including an 8 min gradient). Within the first 2 years, the total number of open‐access analyses increased by ∼125%. It is interesting, however, that the number of LC/MS analyses increased by more than 285%. This is attributed to the fact that the chemists began using the LC/MS data to monitor reactions and also to check final product integrity and purity. In addition, the number of chemists performing parallel synthesis reactions has increased; thus, individual chemists can produce sample sets of up to 100 vials. This paper describes the implementation of new methodology, which accommodates the need for much faster run times and also the ability to acquire alternating positive and negative ion spectra within the same run. In addition, the instrument has been configured to e‐mail the resulting processed data report to the submitting chemist. Several methods have been developed, including structure elucidation using in‐source collision‐induced dissociation (CID) and night‐time analysis. The LC/MS methods for this system are described herein and are applicable to both industrial and academic synthetic chemistry optimization efforts. Copyright © 2002 John Wiley & Sons, Ltd.
Quantitative analysis of the novel depsipeptide anticancer drug Kahalalide F in human plasma by high‐performance liquid chromatography under basic conditions coupled to electrospray ionization tandem mass spectrometry
Authors: Stokvis E. , Rosing H. , López‐Lázaro L. , Rodriguez I. , Jimeno J. M. , Supko J. G. , Schellens J. H. M. , Beijnen J. H. 
Published: October 2002

AbstractKahalalide F (KF) is a novel cyclic depsipeptide anticancer drug, which has shown anticancer activity both in vitro and in vivo especially against human prostate cancer cell lines. To characterize the pharmacokinetics of KF during a phase I clinical trial in patients with androgen refractory prostate cancer, a method was developed and validated for the quantitative analysis of KF in human plasma using high‐performance liquid chromatography (HPLC) coupled to positive electrospray ionization tandem mass spectrometry (ESI‐MS/MS). Microbore reversed‐phase liquid chromatography (LC) performed with mobile phases containing trifluoroacetic acid, an additive commonly used for separating peptides, resulted in substantial suppression of the signal for KF on ESI‐MS/MS. An alternative approach employing a basic mobile phase provided an excellent response for KF when detected in the positive ion mode. Plasma samples were prepared for LC MS/MS by solid‐phase extraction on C18 cartridges. The LC separation was performed on a Zorbax Extend C18 column (150 × 2.1 mm i.d., particle size 5 µm) with acetonitrile –10 mM aqueous ammonia (85 : 15, v/v) as the mobile phase, at a flow‐rate of 0.20 ml min−1. A butyric acid analogue of KF was used as the internal standard. The lower limit of quantitation (LLQ) using a 500 µl sample volume was 1 ng ml−1 and the linear dynamic range extended to 1000 ng ml−1. The inter‐assay accuracy of the assay was −15.1% at the LLQ and between −2.68 and −9.05% for quality control solutions ranging in concentration from 2.24 to 715 ng ml−1. The inter‐assay precision was 9.91% or better at these concentrations. The analyte was stable in plasma under all relevant conditions evaluated and for a period of 16 h after reconstituting plasma extracts for LC analysis at ambient temperature. Copyright © 2002 John Wiley & Sons, Ltd.
Analysis of circular waveguide filter using enhanced FDTD
Authors: Railton Chris J. , Paul Dominique L. 
Published: October 2002

AbstractThe finite difference time domain (FDTD) analysis of iris‐coupled circular waveguide filters presents several challenges because they contain curved metal surfaces and electrically small slots. In this contribution it is shown that by enhancing the basic FDTD algorithm in three ways, filters of this type may be accurately characterized without the need for a highly dense mesh. The enhancements are: (i) an existing locally conformal mesh algorithm to model the curved metal surface, (ii) novel empirical correction factors to account for the singular field behaviour near the slots and their exact position relative to the FDTD cells and (iii) compensation for the numerical dispersion in the FDTD algorithm. The calculation of the correction factors and the implementation of the technique is discussed and the extent to which each of these three enhancements contributes to the reduction of numerical error is shown. In addition, it is shown that a novel combination (i) and (ii) leads to a robust and effective method of treating metal edges which are offset from the edges of the cells. The improvement obtained for a complete filter is demonstrated by comparison to measured results. Copyright © 2002 John Wiley & Sons, Ltd.
Higher order explicit time integration schemes for Maxwell's equations
Authors: Spachmann Holger , Schuhmann Rolf , Weiland Thomas 
Published: October 2002

AbstractThe finite integration technique (FIT) is an efficient and universal method for solving a wide range of problems in computational electrodynamics. The conventional formulation in time‐domain (FITD) has a second‐order accuracy with respect to spatial and temporal discretization and is computationally equivalent with the well‐known finite difference time‐domain (FDTD) scheme. The dispersive character of the second‐order spatial operators and temporal integration schemes limits the problem size to electrically small structures. In contrast higher‐order approaches result not only in low‐dispersive schemes with modified stability conditions but also higher computational costs. In this paper, a general framework of explicit Runge–Kutta and leap‐frog integrators of arbitrary ordersNis derived. The powerful root‐locus method derived from general system theory forms the basis of the theoretical mainframe for analysing convergence, stability and dispersion characteristics of the proposed integrators. As it is clearly stated, the second‐ and fourth‐order leap‐frog scheme are highly preferable in comparison to any other higher order Runge–Kutta or leap‐frog scheme concerning stability, efficiency and energy conservation. Copyright © 2002 John Wiley & Sons, Ltd.
FDTD, multiple‐region/FDTD, ray‐tracing/FDTD: a comparison on their applicability for human exposure evaluation
Authors: Bernardi P. , Cavagnaro M. , D'Atanasio P. , Di Palma E. , Pisa S. , Piuzzi E. 
Published: October 2002

AbstractIn this paper, the finite‐difference time‐domain (FDTD), multiple‐region/FDTD (MR/FDTD) and ray‐tracing/FDTD (RT/FDTD) techniques have been compared with reference to the study of the field scattered by and induced inside an exposed target. The three techniques have been validated on a free‐space radiation problem through a comparison with the MoM solution. Compression techniques have been implemented to obtain a reduction of the computational costs associated with MR/FDTD, performing an accurate evaluation of the associated errors. The applicability and accuracy of the three techniques have then been tested studying the exposure of a sphere to a half‐wavelength dipole. The obtained results have shown that the best computational performances are achieved employing RT/FDTD. However, this technique gives accurate results only in the radiative far‐field of the antenna. MR/FDTD, instead, gives accurate predictions of field distributions for a wide range of distances between the scatterer and the antenna and, thanks to the introduction of compression techniques, requires acceptable computational costs. Pure FDTD, finally, is the most suitable technique, among the three considered, when the scatterer is close to the antenna but its computational costs become prohibitive for large‐scale problems. Copyright © 2002 John Wiley & Sons, Ltd.
Blockade by N‐methyl‐D‐aspartate of elevation of activator protein‐1 binding after stress in rat adrenal gland
Authors: Hinoi Eiichi , Fujimori Sayumi , Yoneyama Masanori , Yoneda Yukio 
Published: October 2002

AbstractCold immobilization stress induced a marked elevation of expression of activator protein‐1 (AP1) complex in rat hypothalamus, pituitary, adrenal, and gastric mucosa, but not in other discrete brain structures examined, when determined immediately after stress for 3 hr. Adrenal AP1 binding linearly increased with the duration of stress up to 6 hr, whereas the increase was seen in both adrenal cortex and medulla of rats stressed for 3 hr. In adrenals, the elevation exhibited decline profiles different from those of expression of cAMP response element binding protein. Western blotting revealed that stress for 3 hr induced significant increases in expression of the components of AP1 complex, c‐Fos, c‐Jun, and Jun‐B proteins, in adrenals, without markedly affecting expression of Fos‐B, Fra‐2, and Jun‐D proteins. The prior systemic administration of N‐methyl‐D‐aspartate (NMDA) led to significant prevention of the elevation after stress for 3 hr in adrenals, whereas the NMDA antagonist dizocilpine alone induced a marked increase in adrenal AP1 binding, without altering the elevation by stress. These results suggest that stress may modulate de novo protein synthesis at the level of gene transcription by AP1 complex through a molecular mechanism associated with NMDA receptor channels in rat adrenal glands. © 2002 Wiley‐Liss, Inc.
Low‐density lipoprotein receptor‐related protein mediates in PC12 cell cultures the inhibition of nerve growth factor‐promoted neurite outgrowth by pregnancy zone protein and α2‐macroglobulin
Authors: Chiabrando Gustavo A. , Sánchez María C. , Skornicka Erin L. , Koo Peter H. 
Published: October 2002

AbstractHuman pregnancy zone protein (PZP) is a major pregnancy‐associated plasma protein closely related to human α2‐macroglobulin (α2M). It has been demonstrated that monoamine‐activated forms of human and rat α2M and rat α1M can bind to TrkA and, respectively, inhibit and stimulate NGF‐promoted neurite outgrowth, Trk phosphorylation, and intracellular signal transduction in PC12 cells. However, the effect of PZP on neurons is unknown, and the molecular mechanism of neuroinhibition by monoamine‐activated α2M is still unclear. In this report, we show that methylamine‐activated PZP (MA‐PZP), like MA‐α2M, inhibits in a dose‐dependent way the NGF‐promoted neurite extension and TrkA phosphorylation in PC12 cells. On the other hand, normal PZP (N‐PZP) had little or no effect. In addition, the inhibitory effect of activated α‐macroglobulins (αMs) was reversible upon its removal from the cell culture. In addition, PZP, as well as α2M, is neuroinhibitory without being directly cytotoxic. It is known that the activated αMs bind to the multiligand receptor termed low‐density lipoprotein receptor‐related protein (LRP) and that the receptor‐associated protein (RAP) specifically blocks uptake of all known LRP ligands. To investigate the potential role of LRP in neuromodulation by activated PZP/α2M, the effect of RAP on the neuroinhibitory activities of these αMs was also studied. Data presented here show that RAP blocked the neurite‐ and Trk‐inhibitory activities of both MA‐PZP and MA‐α2M, whereas RAP itself had no neuromodulatory effect. Hence, we conclude that these data suggest that the LRP receptor and its αM ligands may play a role in regulating Trk receptors. © 2002 Wiley‐Liss, Inc.
Methamphetamine activates DNA binding of specific redox‐responsive transcription factors in mouse brain
Authors: Lee Yong Woo , Son Kwang Won , Flora Govinder , Hennig Bernhard , Nath Avindra , Toborek Michal 
Published: October 2002

AbstractCellular oxidative stress and alterations in redox status can be implicated in methamphetamine (METH)‐induced neurotoxicity. To elucidate the molecular signaling pathways of METH‐induced neurotoxicity, we investigated the effects of a single intraperitoneal injection of METH (1.0, 10, or 20 mg/kg) on DNA‐binding activity of specific redox‐sensitive transcription factors in mouse brain. Transcription factors studied included activator protein‐1 (AP‐1), nuclear factor‐κB (NF‐κB), cAMP‐responsive element‐binding protein (CREB), SP‐1, and signal transducers and activators of transcription (STAT1 and STAT3). Significant and dose‐dependent inductions of AP‐1 and CREB DNA‐binding activities were observed in four different regions (striatum, frontal cortex, hippocampus, and cerebellum) isolated from the brains of mice injected with METH. However, injections with METH did not affect DNA binding activities of NF‐κB, SP‐1, STAT1, and STAT3. These results suggest that METH‐induced oxidative stress may trigger the molecular signaling pathways via specific and selective activation of AP‐1 and CREB. © 2002 Wiley‐Liss, Inc.