bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification of human UDP‐glucuronosyltransferase enzyme(s) responsible for the glucuronidation of 3‐hydroxydesloratadine
Authors: Ghosal Anima , Yuan Yuan , Hapangama Neil , Su Ai Duen (Iris) , Alvarez Narciso , Chowdhury Swapan K. , Alton Kevin B. , Patrick James E. , Zbaida Shmuel
Published: June 2004

Desloratadine is a non‐sedating antihistamine recently approved for the treatment of seasonal allergic rhinitis. The major metabolite of desloratadine in human plasma and urine is the glucuronide conjugate of 3‐hydroxydesloratadine. 3‐Hydroxydesloratadine‐glucuronide is also the major in vitro metabolite of 3‐hydroxydesloratadine formed by incubation of 3‐hydroxydesloratadine with human liver microsomes supplemented with uridine 5′‐diphosphate‐glucuronic acid (UDPGA). The metabolite structure was confirmed by LC‐MS and LC‐MS/MS. Out of ten recombinant human UDP‐glucuronosyltransferases (UGTs), UGT1A1, UGT1A3, UGT1A8 and UGT2B15 exhibited catalytic activity with respect to the formation of 3‐hydroxydesloratadine‐glucuronide. Inhibition studies with known inhibitors of UGT (diclofenac, flunitrazepam and bilirubin) confirmed the involvement of UGT1A1, UGT1A3 and UGT2B15 in the formation of 3‐hydroxydesloratadine‐glucuronide. The results from this study demonstrated that the in vitro formation of 3‐hydroxydesloratadine‐glucuronide from 3‐hydroxydesloratadine was mediated via UGT1A1, UGT1A3 and UGT2B15 in human liver. Copyright © 2004 John Wiley & Sons, Ltd.
Absorption, distribution, metabolism and excretion of YM466, a novel factor Xa inhibitor, in rats
Authors: Mano Yuji , Sonoda Takuya , Nakamura Eiji , Usui Takashi , Kamimura Hidetaka
Published: June 2004

YM466 is a novel factor Xa inhibitor for the treatment of thrombosis. The absorption, distribution, metabolism and excretion of YM466 were investigated in male Fisher rats after a single oral administration. YM466 was absorbed rapidly from all segments of the gastrointestinal tract except the stomach. After oral dosing, the plasma concentration of 14C‐YM466 reached a maximum within 0.5h, and declined rapidly with an elimination half‐life of 0.64h. The unchanged YM466 accounted for almost all of its radioactivity, suggesting a minimal metabolism in rats. This was also supported by the finding that no metabolites were observed in bile and urine after oral dosing of 14C‐YM466. The distribution of 14C‐YM466 in tissue was evaluated and the liver and kidney were the organs with radioactivity concentrations consistently higher than that of plasma. Cumulative biliary and urinary excretion of radioactivity in bile duct‐cannulated rats was 29.5% and 7.6%, respectively, indicating prominent excretion into bile after oral dosing. This was consistent with the finding that 76.1% and 25.2% of radioactivity dosed were excreted to faeces and urine, respectively, after i.v. dosing. These results suggest that YM466 was rapidly absorbed and then subjected to biliary excretion with a minimal metabolism after oral dosing to rats. Copyright © 2004 John Wiley & Sons, Ltd.
Pharmacokinetics and dose proportionality of extended‐release metformin following administration of 1000, 1500, 2000 and 2500 mg in healthy volunteers
Authors: Cullen Edward , Liao James , Lukacsko Peter , Niecestro Robert , Friedhoff Lawrence
Published: June 2004

The pharmacokinetics and dose‐exposure relationship of an extended‐release formulation of metformin (ER‐metformin) was investigated in a randomized, single‐dose, four‐period crossover study in 24 healthy male volunteers. During each study period, subjects received a randomly assigned dose containing 1000, 1500, 2000 or 2500 mg metformin. Blood samples were drawn 0–72 h after dosing for pharmacokinetic and dose‐proportionality assessment. Although several pairwise comparisons between dose groups were significant (p<0.05) with respect to dose‐normalized Cmax, AUC0–72 h, and AUC∞, the magnitude of the difference across the dose range was <20% for AUC0–72 h and AUC∞, and was ⩽30% for Cmax. The results indicate a consistent and predictable increase in metformin exposure with an extended‐release formulation of metformin over 1000 to 2500 mg. Copyright © 2004 John Wiley & Sons, Ltd.
Vasoactive exposures, vascular events, and hemifacial microsomia
Authors: Werler Martha M. , Sheehan Jane E. , Hayes Catherine , Mitchell Allen A. , Mulliken John B.
Published: June 2004

BACKGROUND

Based on experimental evidence and clinical observations, hemifacial microsomia (HFM) is one of several structural anomalies that are postulated to result from vascular disruption. We collected data in a case‐control study to identify whether vasoactive exposures or vascular events during early pregnancy affect the risk of HFM.

METHODS

Cases with a diagnosis of HFM were identified at craniofacial centers in 26 cities across the United States and Canada, from 1996 to 2002. Controls were matched to cases by age and pediatrician practice. Mothers of 230 cases and 678 controls were interviewed about pregnancy events and exposures. Case and control mothers were compared for early pregnancy use of vasoactive medications, cigarettes, and alcohol; singleton or multiple gestation; and diabetes, hypertension, or vaginal bleeding in the first half of pregnancy.

RESULTS

Odds ratios (ORs) were significantly increased for vasoactive mediation use (OR, 1.9 overall; OR, 4.2 among smokers), multiple gestations (OR, 10.5), and diabetes (OR, 6.0). Vaginal bleeding in the second trimester and heavy alcohol intake were associated with increased risks, but the estimates were based on small numbers and, therefore, are unstable. No associations were observed for cigarette smoking without vasoactive medication use, hypertension, and vaginal bleeding in the first trimester.

CONCLUSIONS

The increased risks of HFM associated with vasoactive medication use, multiple gestations, diabetes, and second trimester vaginal bleeding appear collectively to support the hypothesis that vascular disruption is one etiology for HFM, because each of these factors is related to effects on blood vessels. Birth Defects Research (Part A), 2004. © 2004 Wiley‐Liss, Inc.
Base hydrolysis of phosphodiester bonds in pneumococcal polysaccharides
Authors: Pujar Narahari S. , Huang Ngan Fong , Daniels Christopher L. , Dieter Lance , Gayton Marshall G. , Lee Ann L.
Published: June 2004

A comprehensive study of the base hydrolysis of all phosphodiester bond‐containing capsular polysaccharides of the 23‐valent pneumococcal vaccine is described here. Capsular polysaccharides from serotypes 6B, 10A, 17F, 19A, 19F, and 20 contain a phosphodiester bond that connects the repeating units in these polysaccharides (also referred to as backbone phosphodiester bonds), and polysaccharides from serotypes 11A, 15B, 18C, and 23F contain a phosphodiester bond that links a side chain to their repeating units. Molecular weight measurements of the polysaccharides, using high performance size exclusion chromatography with tandem multiangle laser light scattering and refractive index detection, was used to evaluate the kinetics of hydrolysis. The measurement of molecular weight provides a high degree of sensitivity in the case of small extents of reaction, thus allowing reliable measurements of the kinetics over short times. Pseudo‐first‐order rate constants for these polysaccharides were estimated using a simple model that accounts for the polydispersity of the starting sample. It was found that the relative order of backbone phosphodiester bond instability due to base hydrolysis was 19A > 10A > 19F > 6B > 17F, 20. Degradation of side‐chain phosphodiester bonds was not observed, although the high degree of sensitivity in measurements is lost in this case, due to the low contribution of the side chains to the total polysaccharide molecular weight. In comparison with literature data on pneumococcal polysaccharide 6A, 19A was found to be the more labile, and hence appears to be the most labile pneumococcal polysaccharide studied to date. The rate of hydrolysis increased at higher pH and in the presence of divalent cation, but the extent was lower than expected based on similar data on RNA. Finally, the differences in the phosphodiester bond stabilities were analyzed by considering stereochemical factors in these polysaccharides. These results also provide a framework for evaluation of molecular integrity of phosphodiester‐bond‐containing polysaccharides in different solution conditions. © 2004 Wiley Periodicals, Inc. Biopolymers, 2004
Spherical Double Electric Layer Structure and Unprecedented High Stability of the P20O20 Cage and Its Anionic Endohedral Complex Na‐@P20O20
Authors: Wang Yanjin , Xu Jinquan , Cao Zexing , Zhang Qianer
Published: June 2004

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[SiAu4]: Aurosilane.
Authors: Kiran Boggavarapu , Li Xi , Zhai Hua‐Jin , Cui Li‐Feng , Wang Lai‐Sheng
Published: June 2004

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Experimental Coordination Environment of Uranyl(VI) in Aqueous Solution.
Authors: Neuefeind J. , Soderholm L. , Skanthakumar S.
Published: June 2004

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Crystal Structures of the LnAlSi and LnAlGe Compounds.
Authors: Pukas Svitlana , Lutsyshyn Yuri , Manyako Mykola , Gladyshewskii Evgen
Published: June 2004

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Crystal Structure of the Compounds LnAl0.5‐xSi0.5+x (Ln: La, Ce, Pr, Nd, Sm, Gd), Ln3Al4Si6 (Ln: La, Pr), and LnAlSi2 (Ln: Pr, Nd).
Authors: Lyaskovska Natalya , Romaniv Oksana , Semus'o Natalya , Gladyshevskii Evgen
Published: June 2004

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Syntheses, Structures, Magnetic Properties, and X‐Ray Absorption Spectra of Carnotite‐Type Uranyl Chromium(V) Oxides: A[(UO2)2Cr2O8] (H2O)n (A: K2, Rb2, Cs2, Mg; n = 0, 4).
Authors: Locock A. J. , Skanthakumar S. , Burns P. C. , Soderholm L.
Published: June 2004

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Asymmetric Michael Reactions of α‐Substituted Acetates with Cyclic Enones Catalyzed by Multifunctional Chiral Ru Amido Complexes
Authors: Ikariya Takao , Wang Hui , Watanabe Masahito , Murata Kunihiko
Published: June 2004

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Ru(III)‐Catalyzed Cyclization of Arene‐Alkene Substrates via Intramolecular Electrophilic Hydroarylation.
Authors: Youn So Won , Pastine Stefan J. , Sames Dalibor
Published: June 2004

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Indium‐Mediated Radical Cyclization of Iodoalkenes and Iodoalkynes with and Without Allylic and Propargylic Leaving Groups.
Authors: Yanada Reiko , Obika Shingo , Nishimori Nobuaki , Yamauchi Masashige , Takemoto Yoshiji
Published: June 2004

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Reactions of 3‐Benzylindole‐2‐carbohydrazides: Synthesis of New 10‐Benzyl‐1,2‐dihydro‐1‐oxo‐1,2,4‐triazino[4,5‐a]indoles and 3‐Benzyl‐2‐(1,3,4‐oxadiazol‐2‐yl)indoles.
Authors: Maddirala Shambabu Joseph , Gokak Vidya S. , Basanagoudar Linganagouda D.
Published: June 2004

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gem‐Dihalocyclopropane Formation by Iron/Copper Activation of Tetrahalomethanes in the Presence of Nucleophilic Olefins. Evidence for a Carbene Pathway.
Authors: Leonel Eric , Lejaye Michael , Oudeyer Sylvain , Paugam Jean Paul , Nedelec Jean‐Yves
Published: June 2004

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Reactions of Complex Ligands. Part 97. Highly Regio‐ and Diastereoselective Chromium(0)‐Catalyzed Cyclopropanation of 1‐Alkoxy‐1,3‐dienes with Diazo Compounds.
Authors: Hahn Norbert D. , Nieger Martin , Doetz Karl Heinz
Published: June 2004

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Microwave‐Accelerated Facile Synthesis of Fused Polynuclear Hydrocarbons in Dry Media by Intramolecular Friedel—Crafts Alkylation.
Authors: Kurteva Vanya B. , Santos Antonio Gil , Afonso Carlos A. M.
Published: June 2004

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(Diacetoxyiodo)benzene—Lithium Bromide as a Convenient Electrophilic Br+ Source.
Authors: Braddock D. Christopher , Cansell Gemma , Hermitage Stephen A.
Published: June 2004

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Hydroformylation in Fluorous Solvents
Authors: Adams Dave J. , Cole‐Hamilton David J. , Hope Eric G. , Pogorzelec Peter J. , Stuart Alison M.
Published: June 2004

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A Cross Metathesis Based Protocol for the Effective Synthesis of Functionalized Allyl Bromides and Chlorides.
Authors: Bandini Marco , Cozzi Pier Giorgio , Licciulli Sebastiano , Umani‐Ronchi Achille
Published: June 2004

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Polymer‐Supported Triphenylphosphine Ditriflate: A Novel Dehydrating Reagent.
Authors: Elson Kathryn E. , Jenkins Ian D. , Loughlin Wendy A.
Published: June 2004

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Regio‐ and Stereoselective Dimerization of Terminal Alkynes to Enynes in InCl3—NaBH4—MeCN System.
Authors: Wang Chun‐Yan , Su Hua , Yang De‐Yu
Published: June 2004

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Isoxazoles as Latent Siloxybutadienes: An Easy Entry to Polyfunctionalized Benzene Systems via Diels—Alder Reaction with Acetylenes.
Authors: Barbero Asuncion , Pulido Francisco J.
Published: June 2004

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Synthesis of 2‐(Arylamino)‐2‐(arylimino)acetamides.
Authors: Langer Peter , Schroeder Rita
Published: June 2004

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Three‐Component Coupling of Aldehyde, Alkyne, and Amine Catalyzed by Silver in Ionic Liquid.
Authors: Li Zigang , Wei Chunmei , Chen Liang , Varma Rajender S. , Li Chao‐Jun
Published: June 2004

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Stereoselective Carbon—Carbon Bond Formation via the Mitsunobu Displacement of Chiral Secondary Benzylic Alcohols.
Authors: Hillier Michael C. , Desrosiers Jean‐Nicolas , Marcoux Jean‐Francois , Grabowski Edward J. J.
Published: June 2004

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A Chemoenzymatic Approach to Optically Active 5‐Hydroxy‐3‐oxo‐carboxylates.
Authors: Xu Chengfu , Zhang Yonghui , Yuan Chengye
Published: June 2004

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Introducing a Novel Class of Four‐Component Reactions.
Authors: Shaabani Ahmad , Teimouri Mohammad Bagher , Bazgir Ayoob , Bijanzadeh Hamid Reza
Published: June 2004

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Amino Acid Mediated Goldberg Reactions Between Amides and Aryl Iodides.
Authors: Deng Wei , Wang Ye‐Feng , Zou Yan , Liu Lei , Guo Qing‐Xiang
Published: June 2004

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γ‐Alkylthio‐γ‐chloro‐α,β‐dicarbonyl Compounds.
Authors: Guseinov F. I. , Burangulova R. N. , Ismailov V. M.
Published: June 2004

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Iodine(III)‐Mediated Preparations of Nitrogen‐Containing Sulfur Derivatives: Dramatic Influence of the Sulfur Oxidation State.
Authors: Leca Dominique , Song Kai , Amatore Muriel , Fensterbank Louis , Lacote Emmanuel , Malacria Max
Published: June 2004

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Direct Formation of Benzoins from Diarylmethanones via a Rearrangement Reaction Promoted by Samarium Metal in DMF.
Authors: Liu Yongjun , Xu Xiaoliang , Zhang Yongmin
Published: June 2004

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A Novel Synthesis of Parent Resorc[4]arene and Its Partial Alkyl Ethers.
Authors: Stursa Jan , Dvorakova Hana , Smidrkal Jan , Petrickova Hana , Moravcova Jitka
Published: June 2004

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Influence of 2‐Aryl‐3‐halogen/3‐hydroxy‐1,4‐naphthoquinones with Salicylic and Cinnamic Acid Partial Structures on the Arachidonic Acid Cascade. Part 29.
Authors: Richwien A. , Wurm G.
Published: June 2004

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Straightforward Asymmetric Entry to Highly Functionalized 3‐Substituted 3‐Hydroxy‐β‐lactams via Baylis—Hillman or Bromoallylation Reactions.
Authors: Alcaide Benito , Almendros Pedro , Aragoncillo Cristina , Rodriguez‐Acebes Raquel
Published: June 2004

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Radical Reactions of 1,4‐Bis(vinylsulfonyl)tetrafluorobenzene with Tetrahydrofuran.
Authors: Amosova S. V. , Gavrilova G. M.
Published: June 2004

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Expeditious Synthesis of 1,2‐Diaminoimidazoles under Solvent‐Free Conditions.
Authors: Attanasi Orazio A. , De Crescentini Lucia , Favi Gianfranco , Filippone Paolino , Mantellini Fabio , Santeusanio Stefania
Published: June 2004

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An Efficient Synthesis of 5‐Aminoimidazol‐2‐ones via Cyclization Reactions of 2‐Aminoacetonitriles and Isocyanates.
Authors: Parcher Benjamin W. , Erion Derek M. , Dang Qun
Published: June 2004

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Synthesis and Biological Activities of 2‐Alkylthio‐5‐furylmethylidene‐4H‐imidazolin‐4‐ones.
Authors: Yang Feng‐Ling , Liu Zhao‐Jie , Huang Xiao‐Bo , Ding Ming‐Wu
Published: June 2004

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DNA Binding Ligands Targeting Drug‐Resistant Gram‐Positive Bacteria. Part 1. Internal Benzimidazole Derivatives
Authors: Moser Heinz E. , et al. et al.
Published: June 2004

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Design and Synthesis of Novel Small Molecule N/OFQ Receptor Antagonists.
Authors: Chen Zhengming , Goehring R. Richard , Valenzano Kenneth J. , Kyle Donald J.
Published: June 2004

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The Synthesis and X‐Ray Crystal Structure of 9‐Carboxyhexahydro‐7‐methoxy‐4a,7‐ethano‐benzopyran‐5‐en‐1‐one.
Authors: Williams Craig M. , Bernhardt Paul V. , Wiedemann Stefan , Barden Michael C.
Published: June 2004

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InCl3‐Catalyzed Tandem Michael/Friedel—Crafts Cyclization: A Novel Protocol for Chiral 2,4‐Disubstituted Tetrahydroquinolines.
Authors: Yadav J. S. , Reddy B. V. S. , Padmavani B.
Published: June 2004

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A Convenient Synthesis of Novel Pyrido(1′,2′:1,2)imidazo[5,4‐d]‐1,2,3‐triazinones from Imidazo[1,2‐a]pyridines.
Authors: Zamora Hector Salgado , Rizo Benito , Campos Elena , Jimenez Rogelio , Reyes Alicia
Published: June 2004

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Simple Synthesis of Tetrabutylammonium and Potassium Salts of Difluorotriorganostannate and Silicate Anions.
Authors: Bujok Robert , Makosza Mieczyslaw
Published: June 2004

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Scope and Limitations of the Peterson Olefination Reaction as a Route to Vinylidene Phosphanes.
Authors: Izod Keith , McFarlane William , Tyson Brent V.
Published: June 2004

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Magnesium‐Induced Copper‐Catalyzed Synthesis of Unsymmetrical Diaryl Chalcogenide Compounds from Aryl Iodide via Cleavage of the Se—Se or S—S Bond.
Authors: Taniguchi Nobukazu , Onami Tetsuo
Published: June 2004

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Phosphorylated 1,6‐Diphenyl‐1,3,5‐hexatriene.
Authors: Ma Ling , Morgan Jessica C. , Stancill Wendy E. , Allen William E.
Published: June 2004

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Iminosugars from α,β‐Epoxyamides. Part 2. Synthetic Approach to Hydroxylated Pyrrolidine and Azepane Derivatives.
Authors: Assiego C. , Pino‐Gonzalez M. S. , Lopez‐Herrera F. J.
Published: June 2004

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Synthesis of Stavudine Amino Acid Ester Prodrugs with Broad‐Spectrum Chemotherapeutic Properties for the Effective Treatment of HIV/AIDS.
Authors: Sriram Dharmarajan , Yogeeswari Perumal , Srichakravarthy Narasimharaghavan , Bal Tanushree Ratan
Published: June 2004

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Synthesis of (.+‐.)‐Secosyrin 1 and a Formal Synthesis of (‐)‐Secosyrin 1
Authors: Donohoe Timothy J. , Fisher John W. , Edwards Paul J.
Published: June 2004

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Synthesis of Pure Boron Single‐Wall Nanotubes.
Authors: Ciuparu Dragos , Klie Robert F. , Zhu Yimei , Pfefferle Lisa
Published: June 2004

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Magnetism in Nanocrystals
Authors: Hernando A.
Published: June 2004

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Organometallic Chemistry in the Flowing Afterglow: A Review
Authors: Damrauer Robert
Published: June 2004

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Metallosupramolecular Squares: From Structure to Function
Authors: Wuerthner Frank , You Chang‐Cheng , Saha‐Moeller Chantu R.
Published: June 2004

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From Ruthenium(II) to Iridium(III): 15 Years of Triads Based on Bis‐terpyridine Complexes
Authors: Baranoff Etienne , Collin Jean‐Paul , Flamigni Lucia , Sauvage Jean‐Pierre
Published: June 2004

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Excitement in f Block: Structure, Dynamics and Function of Nine‐Coordinate Chiral Lanthanoid Complexes in Aqueous Media
Authors: Parker David
Published: June 2004

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Elongated Dihydrogen Complexes: What Remains of the H—H Bond?
Authors: Heinekey D. Michael , Lledos Agusti , Lluch Jose M.
Published: June 2004

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Recent Development of Peptide Coupling Reagents in Organic Synthesis
Authors: Han So‐Yeop , Kim Young‐Ah
Published: June 2004

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Pd‐Catalyzed Coupling Reactions Involving Propargylic/Allenylic Species.
Authors: Ma Shengming
Published: June 2004

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Indium Salt Promoted Organic Reactions
Authors: Fringuelli Francesco , Piermatti Oriana , Pizzo Ferdinando , Vaccaro Luigi
Published: June 2004

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Organic Conducting Materials, in Particular Polythiophenes
Authors: Schulz Emmanuelle , Lemaire Marc
Published: June 2004

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Azomethine, Carbonyl and Thiocarbonyl Ylides: Generation of Azomethine Ylides from Carbenes and Carbenoids
Authors: Bartnik Romuald
Published: June 2004

For Abstract see ChemInform Abstract in Full Text.
Ammonium, Oxonium, and Sulfonium Ylides: Generation of Oxosulfonium Ylides from Carbenes and Carbenoids
Authors: Ando Wataru , Matsuyama Haruo
Published: June 2004

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Chemical Libraries Towards Protein Kinase Inhibitors
Authors: Kimmich R. D. A. , Park W. K.‐C.
Published: June 2004

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Forward and Reverse Chemical Genetics Using SPOS‐Based Combinatorial Chemistry
Authors: Thorpe David S.
Published: June 2004

For Abstract see ChemInform Abstract in Full Text.
The Total Synthesis of Streptonigrin and Related Antitumor Antibiotic Natural Products.
Authors: Bringmann Gerhard , Reichert Yanina , Kane Vinayak V.
Published: June 2004

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Perfluorinated Polymercuramacrocycles as Anticrowns. Applications in Catalysis.
Authors: Shur V. B. , Tikhonova I. A.
Published: June 2004

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Activation of Carbonyl Compounds by Double Hydrogen Bonding: An Emerging Tool in Asymmetric Catalysis.
Authors: Pihko Petri M.
Published: June 2004

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The Chemical Progress of Multicomponent Reactions
Authors: Ugi Ivar , Ross Guenther , Burdack Christoph
Published: June 2004

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Activating Protecting Groups for the Solid‐Phase Synthesis and Modification of Peptides, Oligonucleotides and Oligosaccharides
Authors: Seitz Oliver
Published: June 2004

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Direct Catalytic Asymmetric Amination of Aldehydes: Synthesis of Evans Oxazolidinones and α‐Amino Acids
Authors: Hughes Chambers C. , Trauner Dirk
Published: June 2004

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Recent Progress in Glycopeptide Synthesis
Authors: Rocchi Raniero , Biondi Laura , Filira Fernando , Gobbo Marina
Published: June 2004

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The Conformational Epitope of Type III Group B Streptococcus Capsular Polysaccharide
Authors: Zou Wei , Jennings Harold J.
Published: June 2004

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Biocatalysis for Sustainable Organic Synthesis
Authors: Sheldon Roger A. , van Rantwijk Fred
Published: June 2004

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Inclusion Complexes of Cyclodextrins in Aqueous Solutions
Authors: Hamai Sanyo , Nakamura Asao
Published: June 2004

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An Introduction to Carbohydrate Synthesis
Authors: Osborn Helen
Published: June 2004

For Abstract see ChemInform Abstract in Full Text.
Fe(III) and Co(III) Centers with Carboxamido Nitrogen and Modified Sulfur Coordination: Lessons Learned from Nitrile Hydratase
Authors: Harrop Todd C. , Mascharak Pradip K.
Published: June 2004

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Charge Transfer and Charge Transport on the Double Helix
Authors: Armitage N. P. , Briman M. , Gruner G.
Published: June 2004

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Structures of Bombyx mori and Samia cynthia Ricini Silk Fibroins Studied with Solid‐State NMR
Authors: Yao Juming , Nakazawa Yasumoto , Asakura Tetsuo
Published: June 2004

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Biogenetic Speculation and Biosynthetic Advances
Authors: Thomas Robert
Published: June 2004

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Artificial Ion Channels
Authors: Stoikov I. I. , Antipin I. S. , Konovalov A. I.
Published: June 2004

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Modern Magnetic Chemistry of Exchange Clusters
Authors: Kalinnikov V. T. , Rakitin Yu. V. , Novotortsev V. M.
Published: June 2004

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Do New Century Catalysts Unravel the Mechanism of Stereocontrol of Old Ziegler—Natta Catalysts?
Authors: Corradini Paolo , Guerra Gaetano , Cavallo Luigi
Published: June 2004

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Use of Cyclodextrins for Separation of Enantiomers
Authors: Shpigun O. A. , Ananieva I. A. , Budanova N. Yu. , Shapovalova E. N.
Published: June 2004

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Ultrasensitive and Quantitative Analyses from Combined Separations — Mass Spectrometry for the Characterization of Proteomes
Authors: Smith Richard D. , Shen Yufeng , Tang Keqi
Published: June 2004

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Non‐Mass‐Dependent Isotopic Fractionation Processes: Mechanisms and Recent Observations in Terrestrial and Extraterrestrial Environments
Authors: Thiemens M. H.
Published: June 2004

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Spin Alignment in the Ground and Excited States on the π‐Conjugated Organic Spin Systems
Authors: Teki Yoshio
Published: June 2004

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The benefit of induction chemotherapy in patients age ≥ 75 years
Authors: Vey Norbert , Coso Diane , Bardou Valerie‐Jeanne , Stoppa Anne‐Marie , Braud Anne‐Chantal , Bouabdallah Reda , Sainty Daniele , Mozziconacci Marie‐Joelle , Lafage Marina , Damaj Gandhi , Blaise Didier , Gastaut Jean‐Albert , Maraninchi Dominique
Published: June 2004

BACKGROUND

Patients age ≥ 75 years with acute myeloid leukemia (AML) generally are offered palliative treatments instead of induction chemotherapy. The authors conducted a retrospective study comparing the outcomes among these elderly patients with the outcomes among younger patients to assess the impact of intensive treatment approaches in this age group.

METHODS

One hundred ten consecutive patients age ≥ 75 years with newly diagnosed AML (excluding patients with acute promyelocytic leukemia) were treated in the authors' center over 10 years. Initial treatment was comprised of anthracycline‐based induction chemotherapy (i.e., intravenous idarubicin or daunorubicin for 3 days plus cytarabine [ARAC] for 7 days [3 + 7 regimen] or oral idarubicin) for 62 patients (56%), antimetabolite‐based chemotherapy (including low‐dose ARAC, oral 6‐mercaptopurine plus methotrexate, or hydroxyurea) for 40 patients (36%), and supportive care only for 8 patients (7%). Results were compared with the results from 200 patients ages 65–74 years who were treated during the same period.

RESULTS

A complete response (CR) to anthracycline‐based induction therapy was achieved by 23 of 62 patients (37%), and the 2‐year overall survival rate was 22% (which was not statistically different from the group of patients ages 65–74 years). In a multivariate analysis of the entire study group (310 patients), treatment (anthracycline‐based vs. other) and age as continuous variable were found to affect survival significantly. In a Landmark analysis, the achievement of a CR translated into improved survival in patients age ≥ 75 years.

CONCLUSIONS

Patients age ≥ 75 years should not be excluded systematically from intensive chemotherapy regimens. Decisions should be based on stratification systems that include functional status and comorbidity assessments as well as prognostic factors, such as cytogenetics. Cancer 2004. © 2004 American Cancer Society.
Synthesis and Reactions of Alkynyl Oligosilanes
Authors: Mechtler Christian , Zirngast Michaela , Baumgartner Judith , Marschner Christoph
Published: June 2004

Synthesis, properties, and reactions of various alkynyl oligosilanes, and their potassium derivatives are described. A series of tris(trimethylsilyl)silylalkynes have been prepared. Their reaction with potassium tert‐butoxide leads to the corresponding potassium derivatives, which can be subjected to further derivatization. X‐ray structures of three oligosilylalkynes are reported. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)
Restricted Phenyl Rotation in Pyridyl Thioether Ligands N,S‐Chelated to Congested Diiminoruthenium Cores
Authors: Baradello Laura , Lo Schiavo Sandra , Nicolò Francesco , Lanza Santo , Alibrandi Giuseppe , Tresoldi Giuseppe
Published: June 2004

The thioethers 2‐pyridylmethyl p‐tolyl sulfide (a) and p‐chlorophenyl 2‐pyridylmethyl sulfide (b) react with the precursors cis‐[RuCl2(N,N‐diimine)2] [diimine = di‐2‐pyridyl sulfide (dps), 1; 2,2′‐bis(4‐methylpyridyl) sulfide (4mdps), 2; 2,2′‐bis(5‐methylpyridyl) sulfide (5mdps), 3; di‐2‐pyrimidyl sulfide (dprs), 4; and 2,2′‐bis(5‐ethylpyrimidyl) sulfide (5edprs), 5] in the presence of NH4PF6 to give the complexes [Ru(N,N‐diimine)2(N,S‐a)][PF6]2 and [Ru(N,N‐diimine)2(N,S‐b)][PF6]2, respectively. As a consequence of the N,S chelation all the complexes contain a five‐membered RuSCCN(Ru−N) ring, the sulfur and ruthenium atoms of which are stereogenic centres, with (R) and (S) and Δ and Λ configurations, respectively. Furthermore, the coordinated thioethers contain anisochronous methylene protons and phenyl protons which are sensor nuclei for pyramidal sulfur inversion and rotation of the pendant phenyl ring, respectively. In the low‐temperature 1H NMR spectra of the complexes a single AB system for the methylene protons, in agreement with a fast sulfur inversion, is observed. Well‐separated signals of the two ortho‐ as well as the meta‐phenyl protons, indicating restricted phenyl rotation, are also observed. At higher temperatures the fast exchange of the two halves of the phenyl ring leads to averaged signals for the phenyl protons. The rates and activation energies of this fluxional process were measured by one‐dimensional band‐shape analysis. Certain trends were immediately apparent. The rotation barrier values (ΔG#298) of the dps, 4mdps and 5mdps complexes were ca. 4.0 kJ·mol−1 lower than those of the dprs and 5edprs complexes. On the contrary, substitution of H4 or H5 dps protons with methyl groups and H5 dprs protons with ethyl groups, as well as substitution of a with b, leaves the rotation‐barrier values practically unchanged. This effect can be correlated to the steric hindrance produced by the two ligands cis to the rotating group. The crystal structure of the enantiomeric couple ΔS/ΛR of [Ru(dps)2(2‐pyridymethyl 2‐pyridyl sulfide)][PF6]2 (1c), in which the 2‐pyrimidylmethyl 2‐pyridyl sulfide (c) ligand acts in an N,S‐bidentate mode forming a five‐membered RuSCCN(Ru−N) chelate ring, is also reported. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)
The Redox Chemistry of SbF6− Ion
Authors: Ponikvar Maja , Liebman Joel F. , Jenkins H. Donald B.
Published: June 2004

Chemical analysis of Sb in coordination compounds requires quantitative reduction of SbV in the form of SbF6− (and its related fluoro‐hydroxy species) to SbIII. This process, although thermodynamically favoured, appears to be kinetically hindered. The experimentally observed stabilisation of SbF6− towards reduction, as happens when the associated metal counterion is complexed by XeF2 (generally regarded as being an oxidizing agent), is also discussed. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)
Tris(pyrazolyl)methane Ligands: Syntheses and Structures of Monometallic and Metallodendritic Complexes
Authors: Sánchez‐Méndez Alberto , Silvestri Gustavo F. , de Jesús Ernesto , de la Mata F. Javier , Flores Juan C. , Gómez Rafael , Gómez‐Sal Pilar
Published: June 2004

The substituted ligands Me3SiC(pz)3 (1) and Me3SiOCH2C(pz)3 (2) have been prepared starting from HC(pz)3 and HOCH2C(pz)3. The molecular structure of compound 1 has been determined by X‐ray diffraction studies, which show a propeller‐like conformation of the pyrazolyl rings. Compound 2 has been found to be useful for the synthesis of [Mo(CO)3{Me3SiOCH2C(pz)3}] (3), [TiCl2(NtBu){Me3SiOCH2C(pz)3}] (4), and [PdCl2{Me3SiOCH2C(pz)3}] (5), through ligand exchange reactions. The characterization of the new complexes is compatible with a tridentate coordination of the ligands in complexes 3 and 4, and a bidentate coordination in 5 as confirmed by an X‐ray analysis carried out with the palladium complex. The procedure has been extended for the synthesis of the carbosilane G1−[OCH2C(pz)3]4 (6) and the tetrametallic compound G1−[OCH2C(pz)3Mo(CO)3]4 (7) (G1 = Si(CH2CH2CH2Me2Si)4−). (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)
Diastereoselection During Allylindium Addition to Norbornyl α‐Diketones
Authors: Khan Faiz Ahmed , Dash Jyotirmayee
Published: June 2004

We report a highly regio‐ and diastereoselective allylindium addition to norbornyl α‐diketones that leads to acyloins. The diastereoselection in the case of monosubstituted derivatives greatly depends on the nature of the 5‐endo substituents. Non‐chelating groups direct the addition from the sterically less congested exo‐face, diagonal to the substituent, while chelating substituents, such as an alkoxy or acetoxy units, induce a complete reversal in the selectivities. The presence of an oxygen atom directly linked to the norbornyl framework is crucial for eliciting a chelating effect because an acetoxymethyl (−CH2OAc) group exhibits normal behavior and acts as a non‐chelating group. The dramatic influence (reversal) of an apparently innocuous exo‐Me substituent is noted. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)
Nitric oxide and p53 in cancer‐prone chronic inflammation and oxyradical overload disease
Authors: Goodman Julie E. , Hofseth Lorne J. , Hussain S. Perwez , Harris Curtis C.
Published: June 2004

Nitric oxide (NO·), which is generated under chronic inflammatory conditions that predispose individuals to cancer, has paradoxical effects. NO· can activate p53, which can result in anti‐carcinogenic effects, or it can be mutagenic and increase cancer risk. We explored the mechanisms by which NO· induced p53 activation in vitro and found that NO· induced p53 accumulation and phosphorylation, particularly at ser‐15, via ATM and ATR kinases, which then led to cell cycle arrest at G2/M. We next examined proteins in these pathways in both inflamed and normal human colon tissue. Inducible nitric oxide synthase (iNOS) levels and p53‐P‐ser15 levels were positively correlated with the degree of inflammation and with each other. Additionally, the p53 targets, HDM‐2 and p21 (WAF1), were present in ulcerative colitis (UC) colon, but undetectable in normal colon, consistent with activated p53. We also found higher p53 mutant frequencies of both G:C → A:T transitions at the CpG site of codon 248 and C:G → T:A transitions at codon 247 in lesional colon tissue from UC cases versus nonlesional tissue from these cases or colon tissue from normal adult controls. Consistent with nitrosative stress and the deamination of 5‐methylcytosine, p53 mutations were also detected in sporadic colon cancer tissue and were associated with iNOS activity in these tissues. These studies identified a potential mechanistic link between NO· and p53 in UC and sporadic colon cancer. Environ. Mol. Mutagen. 44:3–9, 2004. Published 2004 Wiley‐Liss, Inc.
Meat‐related mutagens/carcinogens in the etiology of colorectal cancer
Authors: Cross Amanda J. , Sinha Rashmi
Published: June 2004

Diets containing substantial amounts of red or preserved meats may increase the risk of various cancers, including colorectal cancer. This association may be due to a combination of factors such as the content of fat, protein, iron, and/or meat preparation (e.g., cooking or preserving methods). Red meat may be associated with colorectal cancer by contributing to N‐nitroso compound (NOC) exposure. Humans can be exposed to NOCs by exogenous routes (from processed meats in particular) and by endogenous routes. Endogenous exposure to NOCs is dose‐dependently related to the amount of red meat in the diet. Laboratory results have shown that meats cooked at high temperatures contain other potential mutagens in the form of heterocyclic amines (HCAs) and polycyclic aromatic hydrocarbons (PAHs). To investigate the role of these compounds, we have created separate databases for HCAs and PAHs, which we have used in conjunction with a validated meat‐cooking food frequency questionnaire. The role of meat type, cooking methods, doneness levels, and meat‐cooking mutagens has been examined in both case‐control studies and prospective cohort studies, with mixed results. Here, we review the current epidemiologic knowledge of meat‐related mutagens, and evaluate the types of studies that may be required in the future to clarify the association between meat consumption and colorectal cancer. Environ. Mol. Mutagen. 44:44–55, 2004. Published 2004 Wiley‐Liss, Inc.
Effects of modafinil on cognitive and meta‐cognitive performance
Authors: Baranski Joseph V. , Pigeau Ross , Dinich Peter , Jacobs Ira
Published: June 2004

The stimulant modafinil has proved to be an effective treatment modality for narcolepsy and related sleep disorders and is also being studied for use during sustained military operations to ameliorate the effects of fatigue due to sleep loss. However, a previous study reported that a relatively large, single dose of modafinil (300 mg), administered to already sleep‐deprived individuals, caused participants to overestimate their cognitive abilities (i.e. ‘overconfidence’). Because the predominant application of modafinil is in otherwise healthy, non‐sleep‐deprived individuals, the present study investigated the generality of modafinil‐induced overconfidence in a group of 18 healthy, non sleep‐deprived adults. The design involved a double‐blind, placebo controlled, fully within‐subjects manipulation of placebo and modafinil (4 mg/kg: approximately 300 mg, on average) over three 50‐min cognitive testing sessions (i.e. before drug ingestion, and at 90 and 180 min after drug ingestion). The cognitive task battery included subjective assessments of mood, fatigue, affect, vigor and motivation, and cognitive assessments of serial reaction time, logical reasoning, visual comparison, mental addition and vigilance. In addition, trial‐by‐trial confidence judgements were obtained for two of the cognitive tasks and more global, task level assessments of performance were obtained for four of the cognitive tasks. Relative to placebo, modafinil improved fatigue levels, motivation, reaction time and vigilance. In terms of self‐assessments of cognitive performance, both the placebo and modafinil conditions were ‘well calibrated’ on trial‐by‐trial confidence judgements, showing neither marked over‐ nor under‐confidence. Of note, the modafinil condition displayed a non‐significant tendency towards ‘overconfidence’ for task‐level assessments of performance. The present findings highlight the need for continued research on the many complex interactions involving fatigue states, occasional versus long‐term stimulant use, and subjective assessments of fatigue and cognitive performance. Copyright © 2004 John Wiley & Sons, Ltd.
Topoisomerase‐I, thymidylate synthase primary tumour expression and clinical efficacy of 5‐FU/CPT‐11 chemotherapy in advanced colorectal cancer patients
Authors: Paradiso Angelo , Xu JanMing , Mangia Anita , Chiriatti Annalisa , Simone Gianni , Zito Alfredo , Montemurro Severino , Giuliani Francesco , Maiello Evaristo , Colucci Giuseppe
Published: June 2004

While several studies have reported that thymidylate synthase (TS) tumour expression can be a reliable predictive marker of clinical response to 5‐Fluorouracil (5‐FU) for advanced colorectal cancer patients, only a few studies that searched for predictive factors of irinotecan (CPT‐11) clinical response are available. The aim of the present study has been to verify the predictive value of immunohistochemical topoisomerase‐I (Topo‐I) and TS primary tumour expression in a consecutive series of 62 advanced colorectal cancer patients that received a first line 5‐FU/CPT‐11 chemotherapy. TS and Topo‐I immunostaining was observed in 76% and 43% of tumours, respectively, resulting in a significant relationship within each tumour (r=0.365, p<0.004). Patients with different TS tumour expression showed a similar percentage of Objective Clinical Response, OR (40% vs. 28% of OR in low and high TS‐expressing tumours, respectively, p=ns); also, patients with different Topo‐I tumour expression did not show a different probability of OR (39% vs. 29% of OR in high and low Topo‐I expressing tumours, respectively; p=ns).The tumour expression of these 2 biomarkers also did not impact on time to progression and overall survival of patients. Furthermore, the combined analysis of TS and Topo‐I tumour status did not permit to individualize subgroups of patients with different probability of OR. With multivariate analysis, only patient Performance Status significantly impacted on OS (Hazard ratio 4.87; p=0.02) of these patients. We can conclude that high TS tumour expression seems not to preclude a clinical activity for 5‐FU/CPT‐11 polichemotherapy in advanced colorectal cancer patients; furthermore, clinical response and prognosis of colorectal cancer patients treated with 5‐FU/CPT‐11 regimen do not differ in tumours with different TS or Topo‐I expression. © 2004 Wiley‐Liss, Inc.
Hypermethylation of tumor suppressor genes (p16INK4A, p14ARF and APC) in adenocarcinomas of the upper gastrointestinal tract
Authors: Sarbia Mario , Geddert Helene , Klump Bodo , Kiel Sybille , Iskender Erol , Gabbert Helmut Erich
Published: June 2004

Aberrant promoter methylation is an important mechanism for gene silencing. In the present study, 50 Barrett's esophagus‐associated esophageal adenocarcinomas (ADC), 50 cardiac ADC and 50 gastric ADC were investigated by means of methylation‐specific real‐time PCR for hypermethylation in the tumor suppressor genes APC, p16INk4A and p14ARF. Additionally, expression of p16INK4A protein in the carcinomas was assessed using immunohistochemistry. Marked differences in hypermethylation were found between esophageal, cardiac and gastric ADC in the APC gene (78% vs. 32% vs. 84%) and in the p16INK4A gene (54% vs. 36% vs. 10%). Hypermethylation of p14ARF was absent from esophageal ADC and present infrequently in cardiac (2%) and gastric ADC (10%). Complete loss of p16INK4A protein expression was detectable in 45% of all tumors and was significantly associated with hypermethylation of the p16INK4A gene (p<0.0001, χ2‐test). Our results suggest that hypermethylation of p16INK4A and APC are frequent findings in esophageal, cardiac and gastric ADC. Additionally, the data point to a tumor specific methylation pattern in upper gastrointestinal ADC. © 2004 Wiley‐Liss, Inc.
Anthropometry, breast cancer and menopausal status: Use of repeated measurements over 10 years of follow‐up—results of the French E3N women's cohort study
Authors: Tehard Bertrand , Lahmann Petra H. , Riboli Elio , Clavel‐Chapelon Françoise
Published: June 2004

The association between weight, BMI and breast cancer was analyzed on 94,805 women of the E3N cohort according to their menopausal status. Seven hundred eighty‐six incident invasive premenopausal breast cancers and 1,522 incident invasive postmenopausal breast cancers occurred during a mean follow‐up of 9.7 years. Weight and BMI were updated every 24 months and considered as time‐dependent variables. Data were analyzed using multivariate Cox proportional hazards models. Trend RRs of premenopausal breast cancer were 0.97 (0.92–1.01) for a 5 kg increase in weight and 0.96 (0.91–1.01) for a 2 kg/m2 increase in BMI, adjusted for other known risk factors. Opposite trend RRs were found after menopause: 1.05 (1.02–1.08) for weight and 1.06 (1.02–1.09) for BMI, respectively, for similar increases. Women with a BMI of over 30 kg/m2 had a RR of premenopausal breast cancer of 0.66 (0.40–1.10) compared to those with a BMI of between 18.5 and 25 kg/m2. Postmenopausal women with a BMI of over 30 kg/m2 had a RR of breast cancer of 1.23 (1.00–1.59). The increase in risk of postmenopausal breast cancer with increased weight or BMI was similar whatever the HRT used, although the point estimates were higher in HRT users. We strongly recommend to use anthropometric measurements updated during follow‐up to assess the effect of weight, BMI on breast cancer risk. © 2004 Wiley‐Liss, Inc.
Circulation and homing of melanoma‐reactive T cells to both cutaneous and visceral metastases after vaccination with monocyte‐derived dendritic cells
Authors: Berger Thomas G. , Haendle Ina , Schrama David , Lüftl Matthias , Bauer Nicolas , Pedersen Lars Østergaard , Schuler‐Thurner Beatrice , Hohenberger Werner , Straten Per thor , Schuler Gerold , Becker Jürgen C.
Published: June 2004

Anticancer immune therapies aim at the induction of tumor‐specific T cells, which ultimately should kill tumor cells. The effector cells should, therefore, not only exert cytotoxic activity but also home to and infiltrate the tumor site. Hence, monitoring of immune modulating therapies should not be restricted to the circulating pool of peripheral blood mononuclear cells (PBMC) but also include tumor‐infiltrating lymphocytes (TIL), as well as the correlation of these findings to the clinical course. We report here on the longitudinal immunologic workup of a melanoma patient who developed remarkably potent ex vivo detectable antimelanoma cytotoxic T‐cell (CTL) responses after vaccinations with autologous peptide‐pulsed dendritic cells. Such potent CTL responses to multiple tumor antigens have, to the best of our knowledge, not been described previously in melanoma patients, neither spontaneously nor after any therapy. This patient first experienced a transient response to therapy but finally succumbed to disease progression and died. Progression was associated with the decline of the numbers of tumor‐reactive T cells in circulation and at skin metastases in addition to the loss of MHC class I antigens. The immunologic analysis revealed that fully functional tumor‐specific T cells were present in the peripheral blood of this patient during the phase of a relatively stable disease, and in situ tetramer staining demonstrated that these cells were also accumulated at cutaneous and visceral tumor sites. Furthermore, comparative clonotype mapping of PBMC and TIL depicted an overlapping TCR repertoire usage among these 2 compartments. Since strong CTL responses as observed in this patient are the goal of cancer vaccination but are so far only rarely observed, the thorough analysis of patients exhibiting either exceptional clinical and/or immunologic responses appears critical to understanding how vaccine therapies work and can be further improved. © 2004 Wiley‐Liss, Inc.