bluuebunny/crossref_metadata_2025_split huggingface dataset:
Spinal cord injury‐induced expression of TrkA, TrkB, phosphorylated CREB, and c‐Jun in rat lumbosacral dorsal root ganglia
Authors: Qiao Li‐Ya , Vizzard Margaret A. 
Published: December 2004

AbstractPrevious studies have demonstrated increased expression and phosphorylation of tyrosine kinase receptor (TrkA, TrkB) in lumbosacral DRG after chronic (6 weeks) spinal cord (T8‐T10) injury. This study examined the effects of acute SCI (48 hours, 2 weeks) on TrkA and TrkB expression and phosphorylation, and CREB and c‐Jun expression in DRG. A significant increase in the number of TrkA‐ (1.5–3‐fold; P ≤ 0.05), TrkB‐ (1.3–2.0‐fold; P ≤ 0.05), and phosphorylated Trk (pTrk)‐immunoreactive (1.5–3‐fold; P ≤ 0.05) cells was observed in the L1, L6, and S1 DRG 48 hours, 2, or 6 weeks after SCI. A significant increase in the number of phosphorylated (p‐) CREB‐immunoreactive cells was observed in the L1, L2, L6, and S1 DRG 48 hours, 2, or 6 weeks after SCI. The largest changes in p‐CREB‐immunoreactivity were in L1 and L2 DRG (10‐fold; P ≤ 0.01) at 48 hours after SCI; however, changes were modest in bladder afferent neurons. After SCI, the overall number of c‐Jun‐immunoreactive cells in L1, L2, and S1 DRG was dramatically increased (3–10‐fold; P ≤ 0.01); however, only a low percentage of bladder afferent cells expressed c‐Jun‐IR before or after SCI. In summary, these results suggest that TrkA or TrkB may be involved in reorganization of micturition pathways after SCI. However, CREB or c‐Jun may not be downstream transcription factors in Trk‐mediated signaling cascades in micturition reflex pathways after SCI but may play a role in other, nonbladder SCI‐induced changes. J. Comp. Neurol. 482:142–154, 2005. © 2004 Wiley‐Liss, Inc.
Homogenization of fully nonlinear, uniformly elliptic and parabolic partial differential equations in stationary ergodic media
Authors: Caffarelli Luis A. , Souganidis Panagiotis E. , Wang L. 
Published: December 2004

AbstractWe study the homogenization of fully nonlinear, uniformly elliptic and parabolic second‐order partial differential equations in stationary ergodic media. © 2004 Wiley Periodicals, Inc.
A1 adenosine receptor antagonists, 3‐aryl[1,2,4]triazino[4,3‐a]benzimidazol‐4‐(10H)‐ones (ATBIs) and N‐alkyl and N‐acyl‐(7‐substituted‐2‐phenylimidazo[1,2‐a][1,3,5]triazin‐4‐yl)amines (ITAs): Different recognition of bovine and human binding sites
Authors: Da Settimo Federico , Primofiore Giampaolo , Taliani Sabrina , La Motta Concettina , Novellino Ettore , Greco Giovanni , Lavecchia Antonio , Cosimelli Barbara , Iadanza Manuela , Klotz Karl‐Norbert , Tuscano Daniela , Trincavelli Maria Letizia , Martini Claudia 
Published: December 2004

Abstract3‐Aryl[1,2,4]triazino[4,3‐a]benzimidazol‐4‐(10H)‐ones (ATBIs) 1 and N‐alkyl and N‐acyl‐(7‐substituted‐2‐phenylimidazo[1,2‐a][1,3,5]triazin‐4‐yl)amines (ITAs) 2, recently reported by us as two novel classes of selective A1 adenosine receptor (A1AR) antagonists using bovine cerebral membranes [Da Settimo et al., 2001, Novellino et al., 2002], were reevaluated for their affinity at human A1, A2A, and A3ARs expressed in CHO cells. All the ATBI derivatives 1 showed similar Ki values in the nanomolar range at both hA1AR and bA1AR, with a good selectivity for the hA1AR over the hA2AAR and hA3AR. The excellent correlation between Ki values at hA1AR and bA1AR in the ATBI series suggests that these compounds interact similarly at the binding sites of the two receptors. Unlike findings for the ATBIs 1, the Ki values of ITAs 2 at the hA1AR and bA1AR do not correlate very well. Several compounds (2g, 2i, 2j, 2m, 2n, and 2r) that bind with a nanomolar affinity to the bA1AR were found to be significantly less potent, or even inactive, at the hA1AR. A comparison of the amino acids in the TM regions involved in the recognition of the ligands at the bA1AR and hA1AR failed to provide a clear explanation of the great differences in ligand affinities between bA1AR and hA1AR. Some hypotheses are advanced to account for these differences. Drug Dev. Res. 63:1–7, 2004. © 2004 Wiley‐Liss, Inc.
Therapeutic effects of CPU 86017 on acute and chronic congestive cardiac failure mediated by reducing ET‐1?NOS and oxidative stress in rats
Authors: Wang Yong‐Qing , Shi Yan‐Ping , Dai De‐Zai 
Published: December 2004

AbstractCPU 86017, a derivative of berberine, was administered to rats in which acute and chronic heart failure was induced by left coronary artery ligation for 3 h and 8 weeks, respectively. The rats were divided into the following groups: sham operation, coronary artery ligation (CAL), CAL+ CPU 86017 (80?40 and 20 mg/kg, ig) and CAL+ captopril (60 mg/kg, ig). In the acute model, the systolic parameters of LVSP and LV+dp/dtmax as well as the diastolic parameters of LVEDP and LV‐dp/dtmin improved significantly on pretreatment of CPU 86017 (80 mg/kg). Reductions in elevated serum CPK?LDH?MDA?GOT?GPT?infarcted area and blood viscosity were also significant (P < 0.01). In the chronic model, CPU 86017 (80 mg/kg) preserved the systolic parameters of LVSP and LV+dp/dtmax and the diastolic function of the LVEDP and LV‐dp/dtmin. CPU 86017 completely suppressed elevated plasma ANP and ET‐1, serum and tissue iNOS?NO and MDA, whereas the decreased SOD was improved. CPU 86017 and captopril improved cardiac failure performance and regressed cardiac remodeling in CHF by reducing tissue weight index: lung weight/body weight (BW), right ventricular weight/BW, and left ventricular weight/BW. CPU 86017 exerted beneficial actions in cardiac performance in models of both acute and chronic heart failure, mainly by suppressing ET‐1, iNOS, and oxidative stress in infarcted tissue. Drug Dev Res 63:22–32, 2004. © 2004 Wiley‐Liss, Inc.
Expression genomics and cancer drug development
Authors: Liu Edison T. 
Published: December 2004

AbstractExpression genomics describes the investigation of transcription in a genome‐wide scale, including the study of comprehensive gene regulation. The type of technologies used include microarrays, tag libraries such as serial analysis of gene expression (SAGE), full‐length cDNA cloning and sequencing, chromatin immunoprecipitation coupled with cloning/sequencing or applied to genomic chips [Ruan et al., 2004]. However, since microarrays are the most widely used technology in expression genomics for the study of cancer biology and pharmacology, our discussion will concentrate on studies using expression arrays. Regardless of the methodologies used, information regarding candidate targets, pathways, prognostic markers, and pharmacodynamic responses can be extracted from these experiments. Our premise is that these are powerful tools that can accelerate target identification, validation, and therefore drug discovery. Optimizing this potential will require a different approach to experimental design. Drug Dev. Res. 62:295–302, 2004. © 2004 Wiley‐Liss, Inc.
A new model for utilising chemical diversity from natural sources
Authors: Buss Antony D. , Butler Mark S. 
Published: December 2004

AbstractAlthough combinatorial chemistry technology has enabled large libraries of compounds to be screened for biological activity and synthetic modifications to be effected rapidly, the reality is that quality leads and development candidates for many drug targets still prove difficult to find. This is particularly relevant to antiinfective, oncology, and immunomodulation targets and also those involving protein–protein interactions. In the past, natural products have led to excellent drugs for precisely these therapeutic areas, but the difficulties of identifying and utilising such compounds compared to less complex molecules synthesised using combinatorial chemistry techniques then led many to question their value in modern‐day drug discovery. In fact, in the early 1990s, a significant number of pharmaceutical companies reduced or even terminated the natural product‐based drug discovery activities that had served them so well in the past. Nevertheless a renaissance appears to be at hand. The pressing need to fill drug development pipelines, combined with attractive outsourcing opportunities, have prompted many of the very same companies to reevaluate the utility of natural products as sources of novel drug leads. Through a judicious combination of new technologies and compelling business model, at least one Singapore‐based company is offering cost‐effective solutions for accessing the unique chemical diversity found in Nature. Drug Dev. Res. 62:362–370, 2004. © 2004 Wiley‐Liss, Inc.
Translating the Genome into individualized therapeutics
Authors: Lavedan Christian , Birznieks Gunther , Dressman Marlene , McCullough Karen , Paczkowski Rebecca , Torres Rosa , Wolfgang Curt , Polymeropoulos Mihael 
Published: December 2004

AbstractThe successful completion of the Human Genome Project marked a culmination of numerous advances in genetic research and is viewed as a significant turning point in biology and medicine. Many aspects of medicine and health care may be directly affected by the unraveling of the human genome, including the development of new drugs. Genetic and genomic technologies are being implemented in pharmaceutical and biotechnology companies in search of a competitive advantage in the continual race to discover new therapeutics and bring them to market. These companies are expecting the technologies to enable them to more quickly obtain valuable information on the etiology of diseases, the mechanism of drug action, and treatment response. Successful examples of the implementation of pharmacogenetics and pharmacogenomics have already emerged from the “genome revolution.” The spread of genetic and genomic knowledge throughout all phases of drug development should lead to the successful development of individualized, safer, and more efficacious therapeutics. Ideally, such drugs will maximize therapeutic effects and improve patients' overall quality of life. Drug Dev. Res. 62:371–382, 2004. © 2004 Wiley‐Liss, Inc.
Shape‐mimetics of G‐protein‐coupled receptors in therapeutic drug design and screening
Authors: Sadler Kristen , Tam James P. 
Published: December 2004

AbstractCell surface receptors containing multiple transmembrane (TM) bundles have posed constraints for stable expression of soluble proteins by recombinant methods but created opportunities for synthesis by chemical approaches. The structural restraints imposed by the TM bundles form extracellular loops that can be mimicked by end‐to‐end cyclic peptides. In this paper, we describe an enabling technology that has been designed to exploit a chemical approach for development of cell surface receptor‐mimetics that couple with phage‐display library to obtain biologically active single‐chain antibodies (ScFvs) by an efficient screening method. This approach has been successful in the selection and purification of ScFvs against CCR5, a chemokine receptor critical to HIV infectivity, and holds promise for drug development against other G‐protein‐coupled receptors, including orphan receptors, as well as other receptor proteins anchored by multiple TM helices to the cell surface. Drug Dev. Res. 62:336–348, 2004. © 2004 Wiley‐Liss, Inc.
PLK1 as a potential drug target in cancer therapy
Authors: Goh Kee Chuan , Wang Haishan , Yu Niefang , Zhou Yifa , Zheng Yin , Lim ZeYi , Sangthongpitag Kanda , Fang Lijuan , Du Mark , Wang Xukun , Jefferson A. B. , Rose Janet , Shamoon Blanche , Reinhard Christoph , Carte Brad , Entzeroth Michael , Ni BinHui , Taylor Marcia L. , Stünkel Walter 
Published: December 2004

AbstractPolo‐like kinase 1 (PLK1) has been shown to be involved in cell cycle progression of rapidly proliferating, nontransformed cells as well as tumor cells. In cancer, overexpression of PLK1 contributes to the malignant state by aberrant cell cycle regulation at the G2/M phase. We attempted to validate PLK1 function in cell‐based assays using antisense oligonucleotide knockout approaches. Our own results and published findings of other groups have led to the conclusion that PLK1 is a logical point for pharmacological intervention. HTS campaigns performed against the recombinant PLK1‐protein led to the identification of two PLK1 inhibitory scaffolds, one containing a 7‐azapteridine ring system, the other a fused tetracyclic ketone system. These compounds showed low micromolar antiproliferative activity towards SW620, a human colon cancer cell line, most likely through cell cycle arrest at the G2/M phase. Our data suggest that PLK1 may serve as a target for discovering small molecule anticancer agents. Drug Dev. Res. 62:349–361, 2004. © 2004 Wiley‐Liss, Inc.
New technologies for vaccine development
Authors: Srinivasan Kellathur N. , Brusic Vladimir , August Thomas J. 
Published: December 2004

AbstractVaccines offer protection against infectious diseases, but the successes from the years of development have been mixed. Some diseases have been effectively controlled or eradicated through vaccination, whereas treatments for a number of diseases, especially the reemerging diseases, currently do not exist. Improved understanding of pathogen variability as well as of the diversity of the human immune system, plus technological advances in genetic and molecular biology provide better insights in the host–pathogen interaction and new avenues for vaccine development. In this article we discuss the latest trends in vaccine research with focus on epitope‐based DNA vaccines and trafficking components for efficient vaccine delivery. These approaches are promising in dealing with host and pathogen diversity as well as with diversity within human populations. Drug Dev. Res. 62:383–392, 2004. © 2004 Wiley‐Liss, Inc.
Novel Model Sulfur Compounds as Mechanistic Probes for Enzymatic and Biomimetic Oxidations
Authors: Peñéñory Alicia B. , Argüello Juan E. , Puiatti Marcelo 
Published: December 2004

AbstractTo test for the intermediacy of sulfide radical cations in biomimetic and enzymatic oxidations, the sulfides PhSCH3 (1a), PhSCH2Ph (1b), PhSCHPh2 (1c), PhSCPh3 (1d), CH3SCHPh2 (2), PhSCH2CH=CH2 (3), PhSCH2CH=CHPh (4) and CH3SCH2CH=CHPh (5) were studied, and their results were compared to those obtained for the corresponding chemical electron transfer (CET) and photoinduced electron transfer (PET) oxidations. The radical cations generated from 3−5 by CET in the presence of cerium(IV) ammonium nitrate (CAN) yielded only fragmentation products from the alkyl cations and the thiyl radicals (RS·), whereas 2·+ afforded both fragmentation and mainly α‐deprotonation products. Photochemical treatment of the sulfides 1a and 1b with C(NO2)4 gave only the corresponding sulfoxides, while fragmentation was the main pathway for the photoreactions of 1c, 2 and 5, and for 1d only this latter process was observed. These results support our selection of the sulfides RSCHPh2, RSCH2CH=CHPh (R = Me, Ph) and PhSCPh3 as models for the biomimetic and enzymatic studies. As evidenced by the sulfoxides and sulfones detected as unique products both in protic and in aprotic solvents, it is proposed that the mechanism of the biomimetic sulfoxidations of sulfides 1c and 2−5 by TPPFeIIICl is direct oxygen transfer. Three enzymes − Coprinus cinereus peroxidase (CiP), horseradish peroxidase (HRP) and chloroperoxidase (CPO) − were studied in the oxidation of sulfides 1a, 2, 4 and 5. The use of a racemic alkyl hydroperoxide in the CiP enzymatic oxidation of sulfides 5 and 2 yielded the corresponding sulfoxides (23 and 29%) and the aldehyde or benzophenone (5%), respectively. These results suggest the involvement of an ET process for the CiP‐catalysed oxidation. Fragmentation products were observed in the enzymatic oxidation of sulfide 4 with HRP, which confirms the previously proposed ET mechanism. On the other hand, the CPO‐enzymatic oxidation of sulfide 5 yielded only the corresponding sulfoxide, as would be expected for a direct oxygen‐transfer or oxene mechanism. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)
Synthesis, Characterization, and Thermal Behavior of Steroidal Dendrons
Authors: Ropponen Jarmo , Tamminen Jari , Lahtinen Manu , Linnanto Juha , Rissanen Kari , Kolehmainen Erkki 
Published: December 2004

AbstractA series of novel dendritic steroidal polyesters of first and second generation has been synthesized in convergent fashion by the use of 2,2‐bis(hydroxymethyl)propionic acid as a repeating unit. The first‐ and second‐generation hydroxy‐functionalized dendrons with a variety of surface modifications were produced through the use of four bile acids: lithocholic acid (LCA), ursodeoxycholic acid (UDCA), deoxycholic acid (DCA), and cholic acid (CA). The thermal behavior of the steroidal dendrons was characterized by differential scanning calorimetry (DSC) and by thermogravimetric analysis (TGA). Finally, quantum chemical calculation methods were used to study the geometries of the dendrons and the occurrence of intramolecular hydrogen bonds in these dendritic molecules. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)
Photochromism of Dithienylethenes Containing Fluorinated Thiophene Rings
Authors: Higashiguchi Kenji , Matsuda Kenji , Asano Yukako , Murakami Akinori , Nakamura Shinichiro , Irie Masahiro 
Published: December 2004

AbstractBis(3‐thienyl)perfluorocyclopentenes containing partially fluorinated thiophene rings were synthesized and their behaviors examined. Dithienylethenes containing chlorinated thiophene rings were also prepared as reference compounds. The absorption maxima of the closed‐ring isomers, their thermal stabilities, and their quantum yields varied depending on the substitution position. The absorption maxima showed a red shift upon fluorine substitution at the 2‐ or 4‐positions of the thiophene ring, whereas a blue shift was observed upon substitution at the 5‐position. This shift was explained by the shape of the HOMO and LUMO and was well reproduced by theoretical calculations using time‐dependent density‐functional theory (TD‐DFT). The cycloreversion quantum yield of the closed‐ring isomer of 2‐fluorine‐substituted 1,2‐bis(2‐fluoro‐3‐thienyl)perfluorocyclopentene was about 130 times smaller than that of the closed‐ring isomer of 5‐fluorine‐substituted 1,2‐bis(5‐fluoro‐2‐methyl‐3‐thienyl)perfluorocyclopentene. This low quantum yield was attributed to the change of the π‐conjugation mode in the closed‐ring isomer. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)
In Search of the Weak, Six‐Membered Intramolecular Hydrogen Bond in the Solution and Solid States of Guanidinobenzimidazole
Authors: Chen Jing , Willis Peter G. , Parkin Sean , Cammers Arthur 
Published: December 2004

AbstractThe chemical literature presents evidence for the nonexistence of the intramolecular hydrogen bond in neutral 2‐guanidinobenzimidazole, a result that defies chemical intuition. In the current study, analyses of substituted 2‐guanidinobenzimidazoles by dynamic 1H NMR, IR, and X‐ray diffraction unveiled the contribution of the intramolecular hydrogen bond to the overall structure and conformational equilibria. The presence of the intramolecular hydrogen bond in this work and its absence in previous studies of the unsubstituted parent compound is reconciled by the fact that intramolecular hydrogen bonds between the imidazole moieties and guanidino NH2 protons were weak. The intramolecular hydrogen bonds were more apparent in derivatives with guanidino NHR. The behavior of the latter indicated competition between and coexistence of inter‐ and intramolecular hydrogen bonding. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)
(Trialkoxysilyl)tetrathiafulvalenes: Precursors of Organized Organic‐Inorganic Hybrid Materials by Sol‐Gel Chemistry
Authors: Bellec Nathalie , Lerouge Frédéric , Pichon Benoît , Cerveau Geneviève , Corriu Robert J. P. , Lorcy Dominique 
Published: December 2004

AbstractThe synthesis, characterization and electrochemical behaviour of novel monomers for use in sol‐gel processes are described. These new compounds include a rigid tetrathiafulvalene (TTF) core substituted by one or two spacers, to which a triethoxysilyl group is covalently bonded. The synthesis is based on the preparation of various cyanoethyl‐protected TTF thiolates, deprotection and alkylation of thiolate with 2‐bromoethanol, and subsequent condensation of the alcohol function with 3‐(triethoxysilyl)propyl isocyanate. The donor ability of the title compounds has been investigated by electrochemical studies. The hydrolytic polycondensation of these new precursors was performed in THF solution in the presence of nucleophile (tetrabutylammonium fluoride, TBAF) or acid (HCl) catalysts. The resulting hybrid solids are highly polycondensed and present organization at both the nanometric (X‐ray diffraction) and micrometric (birefringence) scales. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)
Stereoselective Synthesis of 1,2,3‐Trisubstituted 1,3‐Dienes through Novel [3,3]‐Sigmatropic Rearrangements in α‐Allenic Methanesulfonates: Application to the Preparation of Fused Tricyclic Systems by Tandem Rearrangement/Diels−Alder Reaction
Authors: Alcaide Benito , Almendros Pedro , Aragoncillo Cristina , Redondo María C. 
Published: December 2004

AbstractAn unprecedented stereoselective and general synthesis of 1,2,3‐trisubstituted 1,3‐dienes from α‐allenols just by treatment with a methanesulfonyl chloride/tertiary amine system has been developed. This transformation might be tentatively explained in terms of a migration of the methanesulfonyl group in the initially formed α‐allenic methanesulfonate to give the corresponding mesyloxy‐diene through a [3,3]‐sigmatropic rearrangement. This reactivity pattern was incorporated into a domino process, allowing the development of a novel one‐pot synthetic strategy for the preparation of fused tricycles from monocyclic allenols, masked functionalized dienes, when subjected to a domino allenol transposition/intramolecular Diels−Alder reaction process. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)
A Theoretical ab initio Study of the Capacity of Several Binding Units for the Molecular Recognition of Anions
Authors: Garau Carolina , Frontera Antonio , Ballester Pablo , Quiñonero David , Costa Antoni , Deyà Pere M. 
Published: December 2004

AbstractNoncovalent bonding between anions and the π‐cloud of electron‐deficient aromatic rings has recently attracted considerable attention. Complexes of bromide with different electron‐deficient aromatic rings and with other binding units based on hydrogen bonding (urea, thiourea and squaramide) have been studied and compared using high level B3LYP/6‐31++G** ab initio and Molecular Interaction Potential with polarization (MIPp) calculations. Our findings reveal that electron‐deficient aromatic rings are excellent candidates for constructing anion receptors and that the interaction strength can be modulated by the nature of the ring. Supporting experimental evidence has been obtained from X‐ray structures retrieved from the Cambridge Structural Database. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)
A Formal [3 + 3] Cycloaddition Approach to Natural‐Product Synthesis
Authors: Hsung Richard P. , Kurdyumov Aleksey V. , Sydorenko Nadiya 
Published: December 2004

AbstractA formal [3 + 3] cycloaddition strategy for constructing complex heterocycles is reviewed here. This formal cycloaddition involves condensation of α,β‐unsaturated iminium salts with 1,3‐dicarbonyl equivalents. These reactions consist of a Knoevenagel‐type condensation followed by a reversible 6π‐electron electrocyclic ring‐closure. They constitute a stepwise formal [3 + 3] cycloaddition protocol with the net result being the formation of two σ‐bonds in addition to a new stereocenter adjacent to the heteroatom. This review describes in some detail, but not comprehensively, some precedents, problems, solutions, and stereochemical mechanistic issues, and focuses on applications of this formal cycloaddition strategy in natural product synthesis. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)