bluuebunny/crossref_metadata_2025 huggingface dataset:
A nuclear magnetic resonance study of the diastereoisomer complexes formed between a terguride derivative and naproxen
Authors: Castellani Loredana , Flieger Miroslav , Mannina Luisa , Sedmera Petr , Segre Anna Laura , Sinibaldi Massimo
Published: January 2005

1H NMR (600 MHz) measurements of chemical shift changes were made in acidified (DCI) CD3OD/D2O 1:9 v/v equimolar solutions of (S)‐ and (R,S)‐6‐methoxy‐α‐methyl‐2‐naphthaleneacetic acid (naproxen) in the presence of 1‐(3‐aminopropyl)‐(5R,8S,10R)‐terguride (AMP‐TER). The most significant bonding interactions concurring to the formation of diastereoisomer complexes are seen as chemical shifts in proximity to the positively charged nitrogen N(6)‐CH3 and of H(12), H(13), H(14) protons of the ergoline skeleton, both the adducts having an electrostatic term and different π–π stabilizing interactions. Chemical shift data exclude any contribution of the aminopropyl chain to the chiral recognition mechanism. These findings provide an experimental basis for the enantiodiscriminative process accounting for the observed chromatographic resolutions of arylcarboxylic acids on chiral stationary phases derived from AMP‐TER. © 1994 Wiley‐Liss, Inc.
Kinetic resolution of esters of amino acids in t‐butanol containing 5% water catalyzed by a stable industrial alkaline protease
Authors: Chen Shui‐Tein , Huang Wen‐Hong , Wang Kung‐Tsung
Published: January 2005

We developed a procedure for the resolution of esters of amino acids in 95% t‐butanol, followed by saponification of the unreacted esters to afford both enantiomers with high yield and optical purity. The hydrolysis, catalyzed by alkaline protease, was conducted in a mixture of t‐butanol (95%) and water (5%) at 25°C, with a pH controlled at pH 8.5 by the addition of NaOH (2 M). The hydrolyzed L‐amino acid, which was insoluble under these conditions, precipitated during the course of hydrolysis. After separation of the precipitate, the pH of the filtrate was adjusted to 11.5 to saponify the unreacted ester. The D‐antipode precipitated at pH 6.2–6.5. Both optically pure antipodes were obtained with high enantiomeric excesses and yields by simple filtration. © 1994 Wiley‐Liss, Inc.
Assignment of absolute configuration to an improved enantioselective naproxen selector
Authors: Pirkle William H. , Welch Christopher J. , Wilson Scott R.
Published: January 2005

Assignment of absolute configuration to a recently developed chiral selector useful in the separation of the underivatized enantiomers of naproxen and other nonsteroidal anti‐inflammatory drugs (NSAIDs) is described. Circular dichroism, 1H NMR, and X‐ray diffraction have been used to confirm the original assignment which was based solely upon elution orders from HPLC chiral stationary phases. All of these techniques agree in the assignment of the (S,S) absolute configuration to the enantiomer of the chiral selector which associates preferentially with (S)‐naproxen. © 1994 Wiley‐Liss, Inc.
Simultaneous monitoring of the enantiomeric purities of both substrate and product in the enzymatic resolution of (R,S)‐2‐acetoxy‐3‐bromopropyl para‐toluenesulfonate by HPLC chiral column chromatography
Authors: Yin Grace F.S. , Chang Y. G. , Kiang C. M. , Chen G. M.
Published: January 2005

The enantiomeric purities of both substrate, 2‐acetoxy‐3‐bromopropyl para‐toluenesulfonate (I), and product, 2‐hydroxy‐3‐bromopropyl p‐toluenesulfonate (II) were examined in one analysis. The enzymatic resolution was conducted by Amano lipase AK and the enantiomeric excess as well as the conversion rate were monitored by HPLC analysis utilizing a Chiralcel OD column. After 7 h of reaction, HPLC results indicated that the enantiomeric purities of both substrate (I) and product (II) were greater than 95% and the conversion rate was around 55%. © 1995 Wiley‐Liss, Inc.
Protein binding investigation by difference circular dichroism: Native and acetylated human serum albumins
Authors: Bertucci Carlo , Viegi Alessandro , Ascoli Giorgio , Salvadori Piero
Published: January 2005

A modified albumin was prepared by selective reaction of Lys199 with acetyl salicylic acid. Protein binding investigation was carried out on native and modified proteins by difference circular dichroism (ΔCD). Acetylation of Lys199 reduces significantly the effects of the interaction between drugs in the stereoselective HSA binding at specific binding areas. © 1995 Wiley‐Liss, Inc.
The influence of protective groups on diastereofacial selectivity of Diels‐Alder cycloaddition reactions
Authors: Gung Benjamin W. , Mareska David A. , Karipidis Anastas , Henry Thomas
Published: January 2005

The diastereofacial selectivity of both inter‐ and intramolecular Diels‐Alder reactions with dienes having an allylic stereogenic center has been studied by varying the allylic oxygen protective group. Four different hydroxy protective groups were investigated including benzyl, t‐butyldiphenylsilyl, triethylsilyl, and t‐butyldimethylsilyl ethers. For intermolecular reactions, the benzyl ether derivative gave the highest sπ‐facial selectivity through a transition state in which the allylic stereocenter favors the CH eclipsed conformation. For intramolecular cycloadditions, the t‐butyldimethylsilyl group gave a slightly higher selectivity than the benzyl ether derivative through a transition state in which the allylic stereocenter favors the CO eclipsed conformation. The opposite diastereofacial selectivity observed for inter‐ and intramolecular reactions is explained by considering both steric and electronic effects. © 1995 Wiley‐Liss, Inc.
A new approach in exciton‐coupled circular dichroism (ECCD)—insertion of an auxiliary stereogenic center
Authors: Person Richard V. , Monde Kenji , Humpf Hans‐ulrich , Berova Nina , Nakanishi Koji
Published: January 2005

There are cases in which exciton coupling between two chromophores does not occur because the two electric transition moments which should interact are coplanar. This is seen with cyclohexane‐1,4‐diols (both ee or ea) and a wide variety of 3‐hydroxy carotenoids, 3‐hydroxyretinoids, etc. A general approach to deal with such cases is to acylate one of the hydroxyl groups with a chiral allenic acid substituted with a suitable chromophore, e.g., CHROMCHCCH‐COOH. The allenic bond introduces a 90° twist at the italicized central carbon so that the allenic CHROM now couples with the second chromophore. This concept of introducing an auxiliary allenic center should be of general applicability in other similar cases. © 1995 Wiley‐Liss, Inc.
Stereoselective binding of isradipine to human plasma proteins
Authors: Oravcová Jana , Sojková Dagmar , Bencsíková Erika , Bohov Pavol , Trnovec Tomáš
Published: January 2005

Isradipine (PN 200–110) is a highly potent calcium entry blocker with an asymmetrically substituted dihydropyridine ring (methyl‐ and isopropylester, respectively). The binding of the (+)‐(S)‐isradipine and (−)‐(R)‐isradipine to isolated human serum albumin (HSA, 30 μmol/l) and α1‐acid glycoprotein (AAG, 10 μmol/l) has been studied in vitro over a wide range of isradipine concentrations (0.06–20 μmol/l) using high‐performance liquid chromatography (HPLC). HPLC experiments revealed that both isradipine enantiomers were bound to one class of high‐affinity binding sites on the AAG molecule (n(S) = 0.83 ± 0.05, Ka(S) = (1.33 ± 0.25) × 106 1/mol, n(R) = 0.85 ± 0.07, Ka(R) = (1.17 ± 0.44) × 107 l/mol). The (R)‐enantiomer also exhibited an interaction with the secondary low‐affinity binding sites (n′K′a (R) = (2.66 ± 0.65) × 104 l/mol). In contrast, the pharmacologically more potent (+)‐(S)‐enantiomer was more strongly bound to HSA than its optical antipode (n(S) = 1.07 ± 0.07, Ka(S) = (1.76 ± 0.26) × 105 l/mol, nKa(R) = (3.62 ± 0.06) × 104 l/mol). In general, the resulting binding characteristics of individual isradipine enantiomers showed stereoselectivity, but this was opposite for the two most important plasma binding proteins. The process of accumulation of isradipine by human platelets in the therapeutically relevant range (10–80 ng/ml) at 37°C was devoid of stereoselectivity. © 1995 Wiley‐Liss, Inc.
Chiroptical methods in conformational analysis
Authors: Sandström Jan
Published: January 2005

CD spectra of flexible organic molecules in solution are normally very sensitive to conformation. In a system composed of two or more chromophores joined by one or more single bonds and with one fixed or strongly preferred conformation, it is often possible to reproduce the CD spectrum by semiempirical calculations based on interactions between the electronic transitions in the respective chromophores. In a system containing two or more conformations of appreciable weight, the observed CD spectrum is the superposition of those of the individual conformations and has to be analyzed in terms of the individual calculated spectra and the relative energies of the respective conformations. The effect of temperature variation on conformational equilibria and on the composite CD spectra will be discussed and exemplified. © 1995 Wiley‐Liss, Inc.
Chirality induction in cyclocopolymerization of bis(p‐vinylbenzoate)s of carbohydrates with styrene: Chiroptical study of resulting polymer by exciton chirality method
Authors: Haba Osamu , Yokota Kazuaki , Kakuchi Toyoji
Published: January 2005

Three bis(p‐vinylbenzoate) monomers, 2,3‐O‐isopropylidene‐1,4‐bis‐O‐(p‐vinylbenzoyl)‐L‐threitol (BIT), methyl 4,6‐O‐isopropylidene‐2,3‐bis‐O‐(p‐vinylbenzoyl)‐α,D‐glucopyranoside (BIG), and 1,2:5,6‐di‐O‐isopropylidene‐3,4‐bis‐O(p‐vinylbenzoyl)‐D‐mannitol (BIM), were prepared and cyclocopolymerized with styrene. The resulting copolymers were hydrolyzed with KOH to remove the chiral template, and treated with diazomethane to give poly[(methyl p‐vinylbenzoate)‐co‐styrene] [poly(MVB‐co‐St)]. All the poly(MVB‐co‐St) had a specific rotation and their CD spectra exhibit a split Cotton effect. Poly(MVB‐co‐St) derived from poly(BIT‐co‐St) showed a positive Cotton effect at 255 nm and a negative one at 235 nm. According to the exciton chirality method, poly(MVB‐co‐St) possessed negative chirality, and the stereochemistry of the carbon atom attached to the 4‐benzoyl group had the S configuration. The absolute configuration of poly(MVB‐co‐St) was determined as R for the BIG/St system and S for the BIM/St system. © 1995 Wiley‐Liss, Inc.
Degradation and racemization of zopiclone enantiomers in plasma and partially aqueous solutions
Authors: Fernandez Christina , Gimenez François , Mayrargue Joelle , Thuillier Alain , Farinotti Robert
Published: January 2005

We investigated the degradation and racemization of zopiclone (ZOP) enantiomers in plasma and partially aqueous solutions (ethanol:phosphate buffer). Degradation and racemization increased with increasing pH and temperature. Degradation products were identified by means of mass spectrometry, which revealed hydrolysis of the carbamate function and opening of the pyrrolidone ring. In plasma, neither degradation nor racemization occurred after 6 months of storage at ‐20°C and subsequent extraction. © 1995 Wiley‐Liss, Inc.
Substitution and racemization of 3‐hydroxy‐ and 3‐alkoxy‐1,4‐benzodiazepines in acidic aqueous solutions
Authors: Yang Shen K.
Published: January 2005

Oxazepam (OX), 3‐O‐methyloxazepam, 3‐O‐ethyloxazepam, temazepam (TMZ), 3‐O‐methyltemazepam, and 3‐O‐ethyltemazepam underwent acid‐catalyzed nucleophilic substitution reaction (hydrolysis) in an acetonitrile–oxygen‐18 water mixture to form either OX or TMZ in which the 3‐hydroxyl group was either partially or fully labeled with an oxygen‐18 atom. The dependence of the hydrolysis rates on solvent composition, temperature, ionic strength, and in deuterated solvent was studied by reversed‐phase high‐performance liquid chromatography (HPLC). The rates of racemization of enantiomeric compounds in acidic aqueous solutions were studied by both spectropolarimetry and chiral stationary phase HPLC. In acetonitrile: 2.5 M H2SO4 (4:1, v/v) at 50°C, enantiomers of OX and TMZ underwent racemization at rates ≥40‐fold faster than the rates of hydrolysis. Enantiomeric 3‐O‐alkyl derivatives of OX and TMZ in acidic aqueous solutions did not themselves undergo racemization and it was their hydrolysis products (either OX or TMZ) that underwent racemization. © 1995 Wiley‐Liss, Inc.
Inversion of (R)‐ to (S)‐ketoprofen in eight animal species
Authors: Aberg Gunnar , Ciofalo Vincent B. , Pendleton Robert G. , Ray Gene , Weddle Diann
Published: January 2005

The (R)‐enantiomer of the NSAID ketoprofen was administered orally at 20 mg/kg to a series of 8 animal species. In all species, a highly significant degree of inversion occurred after 1 h which varied from 27% (gerbil) to 73% (dog) and persisted or increased in plasma samples obtained 3 h after drug administration. Although the (R)‐enantiomer was inactive as an inhibitor of cyclooxygenase, the analgesic effects of that isomer was almost the same as the (S)‐isomer in animal analgesic assays, following oral administration of the drugs to mice and rats. Taken together, the present results suggest that (R)‐ketoprofen administered alone functioned primarily as a prodrug for (S)‐ketoprofen under the experimental conditions of this study. © 1995 Wiley‐Liss, Inc.
Mechanisms of enantiomeric resolution in cyclodextrin‐modified capillary electrophoretic separations of binaphthyl compounds
Authors: Copper Christine L. , Davis Joe B. , Sepaniak Michael J.
Published: January 2005

The enantiomers of 1,1′‐bi‐2‐naphthol, 1,1′‐binaphthyl diyl hydrogen phosphate, and 1,1′‐binaphthyldicarboxylic acid are separated using capillary electrophoresis with cyclodextrins added to the running buffer. It is demonstrated that the type and concentration of cyclodextrin employed are critical for maximum enantiomeric resolution. A modified version of a previously described model of enantiomeric separations in capillary electrophoresis is shown to support the observed separation behavior. Molecular modeling is employed to calculate interaction energies between the various enantiomers and cyclodextrins. A reasonable correlation between these computationally derived interaction energies and separation behavior resulted from a statistical mechanical treatment of the molecular modeling data. The importance of hydrogen bonding in inclusion complex formation was probed and the effects of minimization and solvation in molecular modeling calculations are also discussed. © 1995 Wiley‐Liss, Inc.
Rapid chiral separation methods development by cyclodextrin‐mediated capillary electrophoresis for acidic and basic compounds
Authors: Guttman András , Brunet Sandra , Jurado Caroline , Cooke Nelson
Published: January 2005

Chiral separation methods development using conventional techniques such as GC or HPLC requires a lot of experience, effort, and expense, due to the wide diversity of the optically active solutes and their possible chiral selectors. Capillary electrophoresis has received increased attention as an alternative technique for chiral separation due to its inherent high efficiencies and ease of methods development. However, due to the wide variety of chiral selectors available in CE, the benefits of this technique might be diminished without an appropriate methods development scheme. In this paper detailed examples are shown for fast, efficient, and predictable chiral capillary electrophoresis separation methods development based on a new and systematic theory. Optimized separations and their parameters are presented for several enantiomeric acids and bases. All the three possible cases, such as the use of low and high pH, as well as pH = pK buffer systems are thoroughly discussed. © 1995 Wiley‐Liss, Inc.
Low configurational stability of amfepramone and cathinone: Mechanism and kinetics of chiral inversion
Authors: Reist Marianne , Christiansen Lisbeth Hein , Christoffersen Pia , Carrupt Pierre‐Alain , Testa Bernard
Published: January 2005

The low configurational stability of two model compounds, the anorectic drug amfepramone and one of its basic metabolites, rac‐cathinone, was examined for its mechanism and kinetics. Assuming a common intermediate for chiral inversion and deuteration, the rates of racemization were determined by the indirect method of proton–deuterium substitution monitored by 1H‐NMR. The rate of racemization increased linearily with increasing pD. At a pD of 7.4, the rate of racemization of both aminoketones was markedly dependent on buffer concentration, indicating a mechanism of general‐base catalysis. The reactions were some five to six times faster in phosphate buffers than in hydroxylamine buffers of identical molarity. Amfepramone racemized about five times faster than the primary amine cathinone. One implication of these findings is that amfepramone and cathinone may be subject in vivo to chiral inversion catalyzed by numerous endogenous bases. As a result, it will be misleading to extrapolate rates of inversion expected in plasma from those measured in buffer solutions. © 1995 Wiley‐Liss, Inc.
Chromatographic resolution of some cyclic sulfoximides derived from prochiral and chiral sulfoxides
Authors: Allenmark Stig , Andersson Christina , Widell Petra
Published: January 2005

Three endocyclic sulfoximides of the 1‐aryl‐ and 1‐alkyl‐3‐oxo‐benzo[d]‐isothia (IV)‐azole 1‐oxide type (1‐substituent = 2′‐carboxyphenyl, 2′‐carbethoxyphenyl, and octyl, respectively) were found to be well resolved on a chiral phase derived from bovine serum albumin (BSA). Selectivities (α) of 1.74, 1.12, and 1.44, respectively, were obtained. The retention behaviour of 1‐octyl‐3‐oxo‐benzo[d]isothia(IV)‐azole 1‐oxide was further investigated in some detail as a function of the mobile phase composition and the elution order was established from optically active material obtained from the enantiopure sulfoxide precursor. An enantiomeric excess of 85.4% was obtained in the cyclocondensation reaction of the octyl‐substituted sulfoxide precursor with hydrazoic acid to the corresponding endocyclic sulfoximide. © 1995 Wiley‐Liss, Inc.
Folding of aminosuccinyl peptides: Thermodynamic data from temperature dependent circular dichroism measurements
Authors: Capasso Sante , Mazzarella Lelio , Zagari Adriana
Published: January 2005

The conformational equilibrium of aminosuccinyl peptides between extended conformations and an intramolecularly hydrogen bonded type II′ β‐turn conformation has been studied on the peptide Boc‐L‐Asu‐Gly‐L‐Ala‐OMe (Asu = aminosuccinyl residue) by means of temperature dependence of circular dichroism spectra.

Owing to the peculiar chiroptical and conformational properties of the Asu residue, this technique proved to be very useful for deriving thermodynamic data for the above folding process. The value of ΔH0 (−6.6 kJ mol−1), obtained for the peptide studied in a chloroformacetonitrile mixture, shows that the lower energy of the folded conformer is primarily due to the characteristic intramolecular hydrogen bond of the β turns. © 1995 Wiley‐Liss, Inc.
Stereoselective pharmacokinetics of oxprenolol, propranolol, and verapamil: Species differences and influence of endotoxin
Authors: Laethem Martine E. , Belpaire Frans M. , Wijnant Pascal , Bogaert Marc G.
Published: January 2005

The influence of endotoxin‐induced inflammation was studied on the pharmacokinetics of the enantiomers of the racemic drugs oxprenolol, propranolol, and verapamil in rabbits and dogs. Enantioselective pharmacokinetics were seen for oxprenolol and propranolol in the rabbit and for propranolol and verapamil in the dog. In the dog, the enantioselective differences in plasma concentrations are due to differences in both protein binding and metabolism, whereas in the rabbit the differences are due solely to differences in metabolism. In both species endotoxin treatment increases the plasma concentrations of the enantiomers of the three drugs; both protein binding and metabolism are influenced. In rabbits and in dogs, the influence of endotoxin on the disposition of the three drugs is less enantioselective than was previously observed in the rat. © 1995 Wiley‐Liss, Inc.
Discrimination in resolving systems II: Ephedrine‐substituted mandelic acids
Authors: Valente Edward J. , Miller Christopher W. , Zubkowski Jeffrey , Eggleston Drake S. , Shui Xiuiqi
Published: January 2005

Binary diastereomeric (‐) (1R,2S)‐ephedrine salts of various mandelic acids obtained from 95% ethanol show considerable differences in solubility. Structures and some properties of the less‐soluble (L) and more‐soluble (M) solid phases of (‐)‐ephedrine with unsubstituted mandelic acid, 2‐, 3‐, and 4‐monosubstituted halo (F, Cl, Br) mandelic acids, and 3‐ and 4‐methylmandelic acids have been determined. Salts were found to be binary, without solvent of crystallization, and composed of double‐layered arrays of alternating anions and cations linked by H‐bonds normal to the layers. H‐bonding links charged donors and acceptors usually along a crystallographic 2‐fold screw axis. A striking discrimination is evident in that the (2R)‐mandelate salts typically display a compact four‐atom chain as the H‐bonding repeating unit [+N—H…O(—C−—O)…H‐N′, C21(4)] while the (2S)‐mandelate salts adopt a more dimensionally variable six‐atom chain repeating unit [+N—H…O—C−—O…H—N′, C22(6)]. Two distinct packing schemes display the shorter H‐bonding chain of the (2R)‐mandelates which always occurs with ephedrinium ions in the fully extended conformation. Slightly greater packing efficiency and H‐bonding energies of the (2R)‐mandelate salts correlates with increased fusion points, lower solubilities (95% ethanol), and higher heats of fusion relative to the phase adopted by their diastereoisomers. In contrast, (2S)‐mandelate salts exhibit considerably more structural variability involving all three major ephedrinium conformations, and at least four distinct packing motifs. Mandelates with larger 3′‐substituents (Cl, Br, methyl) show similar property discriminations, but these occur with an opposing trend, that is, between phases in which the less‐soluble salts contain (2S)‐mandelates. Salts with 2‐bromomandelate do not show property disparities and their structures are dissimilar to the other phases. © 1995 Wiley‐Liss, Inc.
The impact of CAG repeats in exon 1 of the androgen receptor on disease progression after prostatectomy
Authors: Powell Isaac J. , Land Susan J. , Dey Jyotirmoy , Heilbrun Lance K. , Hughes Mark R. , Sakr Wael , Everson Richard B.
Published: January 2005

BACKGROUND

The authors examined the impact of the number of CAG repeats in exon 1 of the androgen receptor on disease progression among men with prostate carcinoma after prostatectomy. This polymorphism has been associated with alterations in activity of the androgen receptor in in vitro systems and with the risk of clinically diagnosed prostate carcinoma in some epidemiologic studies. An earlier series found that, among men at low risk of progressive disease, a small number of CAG repeats predicted a high risk of recurrence, and the impact of CAG repeats varied among men with different risks of progressive disease.

METHODS

The authors analyzed specimens from a large clinical series of fixed tissue specimens from men who underwent prostatectomy at a single institution, including 413 American white men (WM) and 298 African‐American men (AAM), with 5–10 years of available clinical follow‐up.

RESULTS

There was little association between the number of CAG repeats and extent of disease, Gleason score, and preoperative PSA level at diagnosis. Overall, patients who had > 18 CAG repeats had a greater risk of recurrence compared with patients who had ≤ 18 CAG repeats (hazard ratio [HR] = 1.52;P= 0.03). Excess risk was not found among men who were at low risk of recurrence (HR = 0.93;P= 0.96); however, among men who were at high risk of recurrence, the risk elevated for WM (HR = 1.75;P= 0.28), AAM (HR = 1.49;P= 0.06), and both races combined (HR = 1.53;P= 0.03).

CONCLUSIONS

Overall, men with prostate carcinoma who had > 18 CAG repeats had an estimated 52% increased risk of disease recurrence. The increased risk could be attributed to men who were at high risk of recurrence. Cancer 2005. © 2005 American Cancer Society.
Protein expression and gene amplification of epidermal growth factor receptor in thymomas
Authors: Ionescu Diana N. , Sasatomi Elizaburo , Cieply Kathleen , Nola Marin , Dacic Sanja
Published: January 2005

BACKGROUND

Epidermal growth factor receptor (EGFR) overexpression and amplification are important prognostic factors in many solid tumors and anti‐EGFR antibody‐based therapy is now available as a promising therapeutic modality. There is little information in the literature regarding the biologic role of EGFR in thymomas that are characterized by variable clinical presentations, histologic heterogeneity, and unpredictable behavior.

METHODS

Protein expression and gene amplification of EGFR were investigated in 32 thymomas (9 World Health Organization [WHO] type A, 5 type AB, 7 type B2, 7 type B3, 4 type C) using immunohistochemistry and fluorescence in situ hybridization (FISH). FISH analysis included assessment of the average number of copies of the EGFR gene per cell, the average ratio of the EGFR gene to chromosome 7 copy numbers, and ploidy.

RESULTS

The results of FISH analysis showed statistically significant correlation with WHO histologic type, invasion, advanced clinical stage, but not with tumor size and outcome. Thymomas associated with myasthenia gravis more frequently showed hyperploidy when compared with sporadic tumors, but there was no difference in EGFR gene amplification. EGFR protein expression assessed by immunohistochemistry did not correlate with any studied clinicopathologic variables. There was poor correlation between the protein expression and gene amplification, only 7 of 23 specimens (30%).

CONCLUSIONS

The potential role of EGFR in the pathogenesis of advanced‐stage thymomas indicated that evolving anti‐EGFR antibody therapy may be considered as a treatment option. Cancer 2005. © 2005 American Cancer Society.
A multicenter, randomized, Phase II study of cisplatin, etoposide, and gemcitabine or cisplatin plus gemcitabine as first‐line treatment in patients with poor‐prognosis small cell lung carcinoma
Authors: De Marinis Filippo , Nelli Fabrizio , Lombardo Marco , Ferraú Francesco , Barbera Santi , Bertetto Oscar , Barni Sandro , Michetti Giovanni , Labianca Roberto , Gridelli Cesare
Published: January 2005

BACKGROUND

The objective of this study was to evaluate the activity and toxicity of combined cisplatin, etoposide, and gemcitabine (PEG) and combined cisplatin plus gemcitabine (PG) in previously untreated patients with extensive‐stage and poor‐prognosis limited‐stage small‐cell lung carcinoma.

METHODS

One hundred forty patients (70 patients in two arms) were randomized to receive either cisplatin 70 mg/m2 on Day 1, etoposide 50 mg/m2 on Days 1–3, and gemcitabine 1000 mg/m2 on Days 1 and 8 or cisplatin 70 mg/m2 on Day 1 plus gemcitabine 1250 mg/m2 on Days 1 and 8. Both regimens were recycled every 21 days.

RESULTS

In total, 626 cycles were delivered (303 cycles of PEG and 323 cycles of PG), with a median of 4 cycles per patient in both arms. The objective response rate was 63% (95% confidence interval [95%CI], 49–71%) for PEG and 57% (95%CI, 43–67%) for PG, with the suggestion of a higher complete response rate in the PEG arm (18.6% and 4.3%, respectively). A similar time to disease progression (6 months in the PEG arm and 7 months in the PG arm) and a similar median survival (9.5 months in the PEG arm and 10 months in the PG arm) were observed in both arms. The PEG regimen was associated with more severe hematologic toxicity in terms of neutropenia, febrile neutropenia, and a higher rate of treatment delays and dose reductions, whereas nonhematologic toxicities did not differ between the two arms.

CONCLUSIONS

According to the results of this Phase II randomized trial, the PEG regimen produced a higher complete response rate but more toxicity compared with the PG regimen in patients with extensive‐stage or poor‐prognosis, limited‐stage small cell lung carcinoma. Cancer 2005. © 2005 American Cancer Society.
Folding Structures of Isolated Peptides as Revealed by Gas‐Phase Mid‐Infrared Spectroscopy
Authors: Bakker Joost M. , Plützer Christian , Hünig Isabel , Häber Thomas , Compagnon Isabelle , von Helden Gert , Meijer Gerard , Kleinermanns Karl
Published: January 2005

To understand the intrinsic properties of peptides, which are determined by factors such as intramolecular hydrogen bonding, van der Waals bonding and electrostatic interactions, the conformational landscape of isolated protein building blocks in the gas phase was investigated. Here, we present IR‐UV double‐resonance spectra of jet‐cooled, uncapped peptides containing a tryptophan (Trp) UV chromophore in the 1000–2000 cm−1 spectral range. In the series Trp, Trp‐Gly and Trp‐Gly‐Gly (where Gly stands for glycine), the number of detected conformers was found to decrease from six (Snoek et al., PCCP, 2001, 3, 1819) to four and two, respectively, which indicates a trend to relaxation to a global minimum. Density functional theory calculations reveal that the OH in‐plane bending vibration, together with the NH in‐plane bending and the peptide CO stretching vibrations, is a sensitive probe to hydrogen bonding and, thus, to the folding of the peptide backbone in these structures. This enables the identification of spectroscopic fingerprints for the various conformational structures. By comparing the experimentally observed IR spectra with the calculated spectra, a unique conformational assignment can be made in most cases. The IR‐UV spectrum of a Trp‐containing nonapeptide (Trp‐Ala‐Gly‐Gly‐Asp‐Ala‐Ser‐Gly‐Glu) was recorded as well and, although the IR spectrum is less well‐resolved (and it probably results from different isomers), groups of amide I (peptide CO stretching) and amide II (NH in‐plane bending) bands can still be recognised, in agreement with predictions at the AM1 level.
Primary sclerosing cholangitis as a cause of false positive bile duct brushing cytology: Report of two cases.
Authors: Layfield Lester J. , Cramer Harvey
Published: January 2005

Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease of unknown etiology characterized by ongoing inflammation, destruction, and fibrosis of intrahepatic and extrahepatic bile ducts. Irregular narrowing and dilation of the biliary duct system produces the characteristic beaded pattern seen on cholangiogram. Malignant degeneration resulting in cholangiocarcinoma is a well‐recognized sequela of PSC. Bile duct brushing cytology is the primary screening technique for cholangiocarcinoma. It is associated with a relatively low sensitivity but high specificity. Few false positive bile duct brushings have been reported in the literature, with the majority of these having occurred in a background of PSC. We report two patients with PSC in whom bile duct brush cytologies were falsely positive for carcinoma. Diagn. Cytopathol. 2005;32:119–124. © 2005 Wiley‐Liss, Inc.
Evolutionary origin of the feather epidermis
Authors: Sawyer Roger H. , Rogers Loren , Washington Lynette , Glenn Travis C. , Knapp Loren W.
Published: January 2005

The formation of scales and feathers in reptiles and birds has fascinated biologists for decades. How might the developmental processes involved in the evolution of the amniote ectoderm be interpreted to shed light on the evolution of integumental appendages? An Evo–Devo approach to this question is proving essential to understand the observation that there is homology between the transient embryonic layers covering the scale epidermis of alligators and birds and the epidermal cell populations of embryonic feather filaments. Whereas the embryonic layers of scutate scales are sloughed off at hatching, that their homologues persist in feathers demonstrates that the predecessors of birds took advantage of the ability of their ectoderm to generate embryonic layers by recruiting them to make the epidermis of the embryonic feather filament. Furthermore, observations on mutant chickens with altered scale and feather development (Abbott and Asmundson [1957] J. Hered. 18:63–70; Abbott [1965] Poult. Sci. 44:1347; Abbott [1967] Methods in developmental biology. New York: Thomas Y. Crowell) suggest that the ectodermal placodes of feathers, which direct the formation of unique dermal condensations and subsequently appendage outgrowth, provided the mechanism by which the developmental processes generating the embryonic layers diverged during evolution to support the morphogenesis of the epidermis of the primitive feather filament with its barb ridges. Developmental Dynamics 232:256–267, 2005. © 2005 Wiley‐Liss, Inc.
Potential role of thioredoxin in immune responses in intestinal lamina propria T lymphocytes
Authors: Sido Bernd , Giese Thomas , Autschbach Frank , Lasitschka Felix , Braunstein Jutta , Meuer Stefan C.
Published: January 2005

Thioredoxin (TRX) is a ubiquitous oxidoreductase with strong co‐cytokine, chemoattractant and anti‐apoptotic activities. TRX expression was found to be particularly elevated in the intestinal mucosa, where its physiologic function is entirely unknown. Here, we demonstrate a high level of TRX expression in lamina propria T cells (LP‐T) as opposed to autologous peripheral blood T lymphocytes (PB‐T). Addition of recombinant human TRX (rhTRX) to PB‐T enhances TRX gene expression. This autoregulation involves the calcineurin signaling pathway, as rhTRX antagonizes the cyclosporine A (CsA)‐ and tacrolimus‐mediated suppression of TRX gene expression. Similarly, rhTRX reverses the suppression of IL‐2 mRNA production by CsA and enhances cytokine production preferentially in prestimulated cells. The differential TRX expression in LP‐T versus PB‐T may thus contribute to the high‐level, CsA‐resistant IL‐2 production characteristic for CD2‐stimulated LP‐T. Inversely, inactivation of TRX in LP‐T through inhibition of TRX reductase abolishes cytokine gene expression. TRX may play a key role in the specialized intestinal microenvironment in amplifying immediate immune responses of LP‐T whenever appropriate costimulation of LP‐T is provided.
The functional avidity of virus‐specific CD8+ T cells is down‐modulated in Borna disease virus‐induced immunopathology of the central nervous system
Authors: Engelhardt Karin R. , Richter Kirsten , Baur Karen , Staeheli Peter , Hausmann Jürgen
Published: January 2005

Borna disease virus (BDV) infection of the central nervous system (CNS) leads to severe neurological symptoms in susceptible MRL mice. The disease is mainly mediated by CD8+ T cells specific for the immunodominant epitope TELEISSI in the BDV nucleoprotein. In this study, TELEISSI/MHC class I tetramers were used to directly visualize antigen‐specific CD8+ T cells. We found that on average approximately 30% of the ex vivo analyzed CD8+ T cells in the CNS of diseased mice were specific for TELEISSI. Unexpectedly, the frequency of tetramer‐reactive brain‐derived CD8+ T cells doubled following overnight culture in the absence of antigen. The majority of CD8+ T cells showed enhanced tetramer binding without up‐regulation of T cell receptor surface expression. The frequency of IFN‐γ‐secreting CD8+ T cells after antigen‐specific stimulation was higher in overnight cultures than in freshly isolated BDV‐specific brain lymphocytes, and enhanced tetramer binding correlated with elevated sensitivity to lower levels of peptide antigen in cytotoxicity assays. These results indicate that the functional avidity of virus‐specific CD8+ T cells was down‐modulated in vivo. Thus, quantification of tissue‐infiltrating CD8+ T cells by the tetramer technique must be interpreted with caution as it may underestimate the real frequency of antigen‐specific CD8+ T cells.
Synergistic increases in intracellular Ca2+, and the release of MCP‐1, RANTES, and IL‐6 by astrocytes treated with opiates and HIV‐1 Tat
Authors: El‐Hage Nazira , Gurwell Julie A. , Singh Indrapal N. , Knapp Pamela E. , Nath Avindra , Hauser Kurt F.
Published: January 2005

Recent evidence suggests that injection drug users who abuse heroin are at increased risk of CNS complications from human immunodeficiency virus (HIV) infection. Opiate drugs may intrinsically alter the pathogenesis of HIV by directly modulating immune function and by directly modifying the CNS response to HIV. Despite this, the mechanisms by which opiates increase the neuropathogenesis of HIV are uncertain. In the present study, we describe the effect of morphine and the HIV‐1 protein toxin Tat1‐72 on astroglial function in cultures derived from ICR mice. Astroglia maintain the blood‐brain barrier and influence inflammatory signaling in the CNS. Astrocytes can express μ‐opioid receptors, and are likely targets for abused opiates, which preferentially activate μ‐opioid receptors. While Tat alone disrupts astrocyte function, when combined with morphine, Tat causes synergistic increases in [Ca2+]i. Moreover, astrocyte cultures treated with morphine and Tat showed exaggerated increases in chemokine release, including monocyte chemoattractant protein‐1 (MCP‐1) and regulated on activation, normal T cell expressed and secreted (RANTES), as well as interleukin‐6 (IL‐6). Morphine‐Tat interactions were prevented by the μ‐opioid receptor antagonist β‐funaltrexamine, or by immunoneutralizing Tat1‐72 or substituting a nontoxic, deletion mutant (TatΔ31‐61). Our findings suggest that opiates may increase the vulnerability of the CNS to viral entry (via recruitment of monocytes/macrophages) and ensuing HIV encephalitis by synergistically increasing MCP‐1 and RANTES release by astrocytes. The results further suggest that astrocytes are key intermediaries in opiate‐HIV interactions and disruptions in astroglial function and inflammatory signaling may contribute to an accelerated neuropathogenesis in HIV‐infected individuals who abuse opiates. © 2004 Wiley‐Liss, Inc.
sp2‐Hybridized silicon: Parameters for molecular modeling
Authors: Brook A. G. , Gajewski J. J.
Published: January 2005

A set of mutually compatible torsional, stretch, and bending parameters have been devised that reproduce with considerable accuracy the calculated structures of simple silenes and disilenes, and the crystal structure data available for solid silenes and disilenes.
The reactions of tellurium tetrachloride with aliphatic monoketones
Authors: O'Brien Daniel H. , Irgolic Kurt J. , Huang Chang‐Kai
Published: January 2005

The reactions of 13 aliphatic ketones with tellurium tetrachloride has been studied with proton, carbon‐13, and tellurium‐125 NMR. Tellurium tetrachloride adds electrophilically to the α‐carbon of the enol to form ketonyl tellurium trichlorides. Unsymmetric ketones gave mixtures of isomeric ketonyl tellurium trichlorides. Steric hindrance determines which ketonyl tellurium trichlorides form. Except for the ketonyl tellurium trichloride from 2‐butanone, tellurium reacts preferentially with the least substituted α‐carbon. Six methyl alkyl ketones also yielded appreciable amounts of diketonyl tellurium dichlorides. In all diketonyl tellurium dichlorides, tellurium is bonded to less hindered methylene carbons.
Ambident electrophilicity of O,O‐diethyl‐S‐phenyl phosphorothiolate
Authors: Garbers Hendrik V. , Modro Tomasz A.
Published: January 2005

Reaction between O,O‐diethyl‐S‐phenyl phosphorothiolate and lithium dialkylamides results in the displacement of the PhS substituent by the R2N group. With Grignard reagents, the same substrate gives products of the nucleophilic substitution at both the phosphorus and the sulfur atom.
Reaction of (t‐BuGaCl2)2 with Ar′PHLi (Ar′ = 2,4,6‐t‐Bu3C6H2): Preparation of the chloride‐bridged dimer (t‐BuGa(Cl)P(H)Ar′)2
Authors: Cowley Alan H. , Jones Richard A. , Mardones Miguel A. , Atwood Jerry L. , Bott Simon G.
Published: January 2005

The reaction of (t‐BuGaCl2)2 with Ar′P(H)Li (AR′ = 2,4,6‐t‐Bu3C6H2) affords the chloride‐bridged dimer [t‐BuGa(Cl)P(H)Ar′]2 (1). The structure of 1 has been established by X‐ray crystallography. Compound 1, C44H78Cl2Ga2P2, crystallizes in the monoclinic space group P21/n with Z = 2, a = 10.468(1), b = 14.967(1), c = 16.182(2) Å, and Å = 94.48(1)β. The reaction of 1 with t‐BuLi is described.
Efficient deanilidation of phosphoranilidates by the use of nitrites and acetic anhydride
Authors: Nishino Shigeyoshí , Nagato Yasuhiro , Hasegawa Yoshihiro , Yamamoto Hisanao , Kamaike Kazuo , Ishido Yoshiharu
Published: January 2005

Reagent systems of sodium– and tetrabutylammonium nitrite–acetic anhydride were proved to be extremely efficient for the deanilidation of nucleoside 3′‐phosphoranilidates, whose reactions were rapid with the former and instant with the latter. It was further found that the reagent system is applicable to oligonucleotide synthesis provided that the exocyclic amino groups of 2′‐deoxyadenosine, 2′‐deoxyguanosine, and 2′‐deoxycytidine were protected by succinylation.
2‐Aminopyridiniomethylphosphonite: A hydrogen‐bonded polymer from the hydrolysis of 1,3,4‐diazaphospholo[1,2‐a]pyridine
Authors: Litvinov Igor A. , Karaghiosoff Konstantin , Schmidpeter Alfred , Zabotina Elena Y. , Dianova Evelina N.
Published: January 2005

Condensation of 2‐aminopyridine and chloromethyldichlorophosphane yields 1,3,4‐diazaphospholo[1,2‐a]pyridine 2. Methanol adds to 2 while diethylamine does not; with additional elemental sulfur, in both cases the sulfides 4, 6 of the respective adducts are formed. Hydrolysis of 2 specifically opens the PN‐bond and gives the zwitterionic 2‐aminopyridinio‐methylphosphonite 7. The compound crystallizes with one molecule water in the monoclinic space group P21/c with a = 25.490(7)Å, b = 7.365(4)Å, c = 9.088(3)Å, β = 100.06(3)°, and Z = 8 with two independent molecules of 7 and of water. In the crystal hydrogen bonds connect the molecules of 7 to form double‐chain structured polymers. The individual double‐chains are linked to each other by hydrogen‐bonded water molecules.
Synthesis, characterization, and in vitro antitumor activity of some tin(IV)–oxygen and tin(IV)–sulfur heterocycles
Authors: Bouâlam Mohammed , Willem Rudolph , Biesemans Monique , Mahieu Bernard , Gielen Marcel
Published: January 2005

The synthesis of diorganotin(IV) derivatives of thiosalicylic acid, of 3‐aza‐2‐thiosalicylic acid, and of several related compounds is reported. Their characterization by 1H, 13C, and 119Sn NMR, Mössbauer, and mass spectrometry is described. The in vitro antitumor activity of selected derivatives against two human tumoral cell lines is discussed.
Unsymmetrical and symmetrical diphosphazane ligands derived from o‐phenylene phosphorochloridite
Authors: Babu Ruppa P. Kamalesh , Krishnamurthy Setharampattu S. , Nethaji Munirathinam
Published: January 2005

Two new diphosphazane ligands, PriN(PPh2)(PO2C6H4) (1) and PriN{P(O2C6H4)}2 (3), have been synthesized and characterized by spectroscopic data. The structure of 1 has been confirmed by single crystal X‐ray diffraction. Crystal data: Monoclinic, C2/c, Z = 16, a = 34.149(5) Å, b = 9.717(6) Å, c = 29.439(5) Å, β = 125.11(2)°, V = 7991 Å3, R = 0.058, Rw = 0.061. This compound shows two different P–N bond lengths (1.654 (4) and 1.743(4) Å) and a P–N–P angle of 120.7(2)°. Variable temperature 31P NMR measurements for 1 and 3 throw light on the nature of the conformers present in solution.
Sodium arenetellurolate‐catalyzed reduction of nitroalkanes to oximes
Authors: Ohe Kouichi , Uemura Sakae
Published: January 2005

Treatment of aliphatic nitro compounds with NaBH4 in alkaline ethanol in the presence of a catalytic amount of diaryl ditelluride at 25°C for 5–20 h produces the corresponding oximes, generally as a mixture of E/Z isomers, in fair to good yields. Arenetellurolate anion (ArTe−) generated in situ is suggested to be the active species for the reduction.
13C Chemical shifts and 13C15N coupling constants of some 15N‐labelled bridgehead nitro compounds
Authors: Della Ernest W. , Janowski Wit K. , Kasum Bruno , Kirkbride K. Paul , Shirley Neil J.
Published: January 2005

Measurement of the 13C NMR spectra of the bridgehead nitro compounds 1a–5a has been performed. It is found that one‐bond 13C15N coupling is not necessarily a reflection of the degree of s character of the bridgehead carbon exocyclic bonding orbital. Although the magnitude of vicinal coupling to the bridgehead carbon increases, in accordance with the number of three‐bond pathways available for transmission of spin information, coupling is actually reduced by opposing contributions from through‐space intramolecular orbital interactions.
Amperometric enzyme‐modified electrodes based on tetrathiafulvalene derivatives for the determination of glucose
Authors: Lee H. S. , Liu L.‐F. , Hale P. D. , Okamoto Y.
Published: January 2005

A number of tetrathiafulvalene (TTF) derivatives have been synthesized and tested as electron transfer mediators in glucose oxidase‐based amperometric biosensors. Using cyclic voltammetry and stationary potential experiments, it is shown that several of these derivatives can effectively mediate electron transfer from the reduced flavin adenine dinucleotide redox centers of glucose oxidase to a conventional carbon paste electrode. An insoluble polymeric electron relay system, based on the covalent attachment of TTF moieties to a highly flexible siloxane polymer, is also shown to facilitate a flow of electrons from the enzyme to the electrode. The resulting glucose biosensors function efficiently over a clinically relevant range of glucose concentrations.
Cyclic SN compounds and phosphorus reagents: Part X. Synthesis and characterization of phosphinimino‐substituted SN heterocycles
Authors: Thomas C. J. , Rao M. N. Sudheendra
Published: January 2005

Room temperature reactions of S4N4 with (amino) diphenylphosphines, (R)Ph2P, have basically yielded two different types of SN heterocycles under two different stoichiometric conditions. Phosphiniminocyclotrithiatriazenes, (R)Ph2PNS3N3 (R = C4H8N, C5H10N, C6H12N, CH3NC4H8N, (C6H11)2 N, and (C6H5CH2)2N) have been obtained (yield 45–76%) from a 1:2 mole ratio (S4N4:(R)Ph2P) reaction, while the disubstituted S4N4 derivatives, 1,5‐[Ph2(R)PN]2S4N4 (R = C4N8N, C5H10N, and C6H12N) have been obtained (yield 30–45%) only from a 1:3.5–4 mole ratio reaction. All the 1,5‐[Ph2(R)PN]2S4N4 derivatives prepared in this study undergo a room temperature solution phase transformation to the corresponding (R)Ph2PNS3N3 heterocycles.
Ir‐spectroscopic evidence for NaSiO and KSiO in solid argon
Authors: Köppe Ralf , Schnöckel Hansgeorg
Published: January 2005

Condensation of SiO with sodium or potassium, respectively, leads to the formation of Na+(SiO)− and K+(SiO)−. The SiO force constant is reduced to 6.15 mdyn/Å and 6.30 mdyn/Å with respect to uncoordinated SiO (f = 9.0 mdyn/Å). From these results a similar type of bonding can be concluded for the charge transfer complexes Ag+(SiO)− and Ag+(SiS)− published recently.
Proximity effect in the oxidation of dithiols with 3‐methyllumiflavin
Authors: Nagata Toshiyuki , Fujimori Ken , Oae Shigeru
Published: January 2005

Rates of oxidation of various dithiols with 3‐methyllumiflavin to afford the corresponding cyclic disulfides have been examined at various pH values in 30% aqueous ethanol at 30°C. 1,3‐Propanedithiol, which affords 1,2‐dithiolane, has been found to be the most reactive among several dithiols tested in this oxidation. Kinetic results clearly show that highly strained 1,2‐dithiethanes are formed as primary products in the oxidation of vic‐dithiols with 3‐methyllumiflavin.
Stereoselective synthesis of (2Z)‐cinnamanilides via desulfonylation of (2E)‐α‐amido‐α,β‐unsaturated sulfones by sodium hydrogen telluride
Authors: Huang Xian , Pi Jin‐Hong , Huang Zhi‐Zhen
Published: January 2005

(2E)‐α‐Amido‐α,β‐unsaturated sulfones, which are easily prepared by the condensation of α‐amido‐sulfones with aldehydes, can be desulfonylated by sodium hydrogen telluride to give (2Z)‐cinnamanilides with excellent stereoselectivity and in good yields.