bluuebunny/crossref_metadata_2025_split huggingface dataset:
Significance of valine/leucine247 polymorphism of β2‐glycoprotein I in antiphospholipid syndrome: Increased reactivity of anti–β2‐glycoprotein I autoantibodies to the valine247 β2‐glycoprotein I variant
Authors: Yasuda Shinsuke , Atsumi Tatsuya , Matsuura Eiji , Kaihara Keiko , Yamamoto Daisuke , Ichikawa Kenji , Koike Takao 
Published: January 2005

AbstractObjectiveTo clarify the consequences of the valine/leucine polymorphism at position 247 of the β2‐glycoprotein I (β2GPI) gene in patients with antiphospholipid syndrome (APS), by investigating the correlation between genotypes and the presence of anti‐β2GPI antibody. The reactivity of anti‐β2GPI antibodies was characterized using recombinant Val247 and Leu247 β2GPI.MethodsSixty‐five Japanese patients with APS and/or systemic lupus erythematosus who were positive for antiphospholipid antibodies and 61 controls were analyzed for the presence of the Val/Leu247 polymorphism of β2GPI. Polymorphism assignment was determined by polymerase chain reaction followed by restriction enzyme digestion. Recombinant Val247 and Leu247 β2GPI were established to compare the reactivity of anti‐β2GPI antibodies to β2GPI between these variants. The variants were prepared on polyoxygenated plates or cardiolipin‐coated plates, and the reactivity of a series of anti‐β2GPI antibodies (immunized anti‐human β2GPI monoclonal antibodies [Cof‐19–21] and autoimmune anti‐β2GPI monoclonal antibodies [EY1C8, EY2C9, and TM1G2]) and IgGs purified from patient sera was investigated.ResultsA positive correlation between the Val247 allele and the presence of anti‐β2GPI antibodies was observed in the patient group. Human monoclonal/polyclonal anti‐β2GPI autoantibodies showed higher binding to recombinant Val247 β2GPI than to Leu247 β2GPI, although no difference in the reactivity of the immunized anti‐β2GPI between these variants was observed. Conformational optimization showed that the replacement of Leu247 by Val247 led to a significant alteration in the tertiary structure of domain V and/or the domain IV–V interaction.ConclusionThe Val247 β2GPI allele was associated with both a high frequency of anti‐β2GPI antibodies and stronger reactivity with anti‐β2GPI antibodies compared with the Leu247 β2GPI allele, suggesting that the Val247 β2GPI allele may be one of the genetic risk factors for development of APS.
Thrombospondin 1 as an effective gene therapeutic strategy in collagen‐induced arthritis
Authors: Jou I‐Ming , Shiau Ai‐Li , Chen Shih‐Yao , Wang Chrong‐Reen , Shieh Dar‐Bin , Tsai Ching‐Shan , Wu Chao‐Liang 
Published: January 2005

AbstractObjectiveBecause thrombospondin 1 (TSP‐1) inhibits angiogenesis and activates latent transforming growth factor β (TGFβ), a potent immunosuppressive and antiinflammatory cytokine, we investigated the prophylactic and therapeutic effects of TSP‐1 gene transfer in the collagen‐induced arthritis (CIA) model in rats.MethodsAdenoviral vectors encoding mouse TSP‐1 (AdTSP‐1) or β‐galactosidase (AdLacZ) as the control were administered by intraarticular injection into CIA rats. The treated ankles were assessed clinically, radiographically, and histologically. Furthermore, expression levels of TSP‐1, TGFβ, vascular endothelial growth factor (VEGF), and interleukin‐1β (IL‐1β) were examined in the synovial tissue.ResultsIntraarticular administration of AdTSP‐1 reduced the severity of CIA as revealed by examination of the clinical, radiographic, and histologic aspects. Rats treated with AdTSP‐1, as compared with AdLacZ‐treated controls, were found to have fewer blood vessels (mean ± SEM 21.0 ± 0.6 versus 45.3 ± 2.3/mm2; P < 0.001) and lower production of VEGF (17 ± 4 versus 45 ± 10 pg/mg of total protein; P < 0.05) and IL‐1β (374 ± 41 versus 526 ± 39 pg/mg of total protein; P < 0.05), as well as higher levels of TSP‐1 and TGFβ in the synovial tissue.ConclusionDirect intraarticular administration of adenoviral vectors encoding TSP‐1 significantly ameliorated the clinical course of CIA, accompanied by reduction of synovial hypertrophy and fewer blood vessels. These results suggest that TSP‐1 gene therapy may have therapeutic potential for the management of rheumatoid arthritis.
Ambulatory monitoring of physical activity and symptoms in fibromyalgia and chronic fatigue syndrome
Authors: Kop Willem J. , Lyden Angela , Berlin Ali A. , Ambrose Kirsten , Olsen Cara , Gracely Richard H. , Williams David A. , Clauw Daniel J. 
Published: January 2005

AbstractObjectiveFibromyalgia (FM) and chronic fatigue syndrome (CFS) are associated with substantial physical disability. Determinants of self‐reported physical disability are poorly understood. This investigation uses objective ambulatory activity monitoring to compare patients with FM and/or CFS with controls, and examines associations of ambulatory activity levels with both physical function and symptoms during activities of daily life.MethodsPatients with FM and/or CFS (n = 38, mean ± SD age 41.5 ± 8.2 years, 74% women) completed a 5‐day program of ambulatory monitoring of physical activity and symptoms (pain, fatigue, and distress) and results were compared with those in age‐matched controls (n = 27, mean ± SD age 38.0 ± 8.6 years, 44% women). Activity levels were assessed continuously, ambulatory symptoms were determined using electronically time‐stamped recordings at 5 time points during each day, and physical function was measured with the 36‐item Short Form health survey at the end of the 5‐day monitoring period.ResultsPatients had significantly lower peak activity levels than controls (mean ± SEM 8,654 ± 527 versus 12,913 ± 1,462 units; P = 0.003) and spent less time in high‐level activities when compared with controls (P = 0.001). In contrast, patients had similar average activity levels as those of controls (mean ± SEM 1,525 ± 63 versus 1,602 ± 89; P = 0.47). Among patients, low activity levels were associated with worse self‐reported physical function over the preceding month. Activity levels were inversely related to concurrent ambulatory pain (P = 0.031) and fatigue (P < 0.001). Pain and fatigue were associated with reduced subsequent ambulatory activity levels, whereas activity levels were not predictive of subsequent symptoms.ConclusionPatients with FM and/or CFS engaged in less high‐intensity physical activities than that recorded for sedentary control subjects. This reduced peak activity was correlated with measures of poor physical function. The observed associations may be relevant to the design of behavioral activation programs, because activity levels appear to be contingent on, rather than predictive of, symptoms.
Effects of sevelamer and calcium‐based phosphate binders on uric acid concentrations in patients undergoing hemodialysis: A randomized clinical trial
Authors: Garg Jay P. , Chasan‐Taber Scott , Blair Andrew , Plone Melissa , Bommer Juergen , Raggi Paolo , Chertow Glenn M. 
Published: January 2005

AbstractObjectiveGout affects a large fraction of persons with advanced chronic kidney disease, and hyperuricemia may increase the risk of cardiovascular disease. Several hypouricemic agents are contraindicated in patients with end‐stage renal disease. Sevelamer is a nonabsorbed hydrogel that binds phosphorus and bile acids in the intestinal tract. Results of short‐term and open‐label studies suggest that sevelamer might lower the concentration of uric acid, another organic anion. We undertook this study to test our hypothesis that the reduction in serum uric acid concentration induced by sevelamer would be confirmed in a long‐term, randomized, clinical trial comparing sevelamer with calcium‐based phosphate binders.MethodsTwo hundred subjects undergoing maintenance hemodialysis were randomly assigned to receive either sevelamer or calcium‐based phosphorus binders in an international, multicenter, clinical trial. Data on baseline and end‐of‐study uric acid concentrations were available in 169 subjects (85%); the change in uric acid concentration from baseline to the end of the study was the outcome of interest.ResultsBaseline clinical characteristics, including mean uric acid concentrations, were similar in subjects randomly assigned to receive sevelamer and calcium‐based phosphate binders. The mean change in uric acid concentration (from baseline to the end of the study) was significantly larger in sevelamer‐treated subjects (−0.64 mg/dl versus −0.26 mg/dl; P = 0.03). The adjusted mean change in uric acid concentration was more pronounced when the effects of age, sex, diabetes, vintage (time since initiation of dialysis), dialysis dose, and changes in blood urea nitrogen and bicarbonate concentrations were considered (−0.72 mg/dl versus −0.15 mg/dl; P = 0.001). Twenty‐three percent of sevelamer‐treated subjects experienced a study‐related reduction in the concentration of uric acid equal to −1.5 mg/dl or more, compared with 10% of calcium‐treated subjects (P = 0.02).ConclusionIn a randomized clinical trial comparing sevelamer and calcium‐based phosphate binders, treatment with sevelamer was associated with a significant reduction in serum uric acid concentrations.
Annular self‐assembly of DNA molecular chains occurring in natural dry process of diluted solutions
Authors: Morii Nahoko , Kido Giyuu , Suzuki Hiroyuki , Morii Hisayuki 
Published: January 2005

AbstractThe molecular orientation of DNA membranes, which were prepared by subjecting diluted solution of salmon sperm DNA to a natural drying process, was examined. X‐ray diffraction and polarization microscopy revealed that the dried membranes have zonal structures. Each zone shows different features in molecular orientation. In the outer zones formed at the early stage in drying, DNA molecular chains were found to be aligned along the annular curve of the peripheral edge. Both the uneven thickness and disproportional molecular weight distribution in a membrane suggested that the radial flow transported DNA molecules to the edge and that they formed the accumulated phase. Above the critical concentration for the formation of liquid crystalline, the DNA chains would be aligned onto the preformed solid–liquid interface. The membranes with the highest birefringence were obtained from DNA samples with the relatively high molecular weight of around 29 kbp. In the innermost zone, on the other hand, the DNA molecules were radially oriented. This alignment can be attributed to the hydrodynamic effect caused by the rapid translation of the edge interface, which overcomes the Brownian motion of the chain segments. A transitive balance of physical effects was revealed in the dry process, which provided quite orthogonal molecular orientations in a single droplet. © 2005 Wiley Periodicals, Inc. Biopolymers, 2005
Chemical Inhibitors when Timing Is Critical: A Pharmacological Concept for the Maturation of T Cell Contacts
Authors: Köhler Karsten , Lellouch Annemarie C. , Vollmer Susanne , Stoevesandt Oda , Hoff Antje , Peters Lasse , Rogl Hans , Malissen Bernard , Brock Roland 
Published: January 2005

AbstractCellular signal transduction proceeds through a complex network of molecular interactions and enzymatic activities. The timing of these molecular events is critical for the propagation of a signal and the generation of a specific cellular response. To define the timing of signalling events, we introduce the combination of high‐resolution confocal microscopy with the application of small‐molecule inhibitors at various stages of signal transduction in T cells. Inhibitors of Src‐family tyrosine kinases and actin dynamics were employed to dissect the role of the lymphocyte‐specific tyrosine kinase Lck in the formation and maintenance of T cell receptor/CD3‐dependent contacts. Anti‐CD3ε‐coated coverslips served as a highly defined stimulus. The kinetics of the recruitment of the yellow fluorescent protein‐tagged signalling protein ZAP‐70 were detected by high‐resolution confocal microscopy. The analysis revealed that at 5 min after receptor engagement, Lck activity was required for maintenance of contacts. In contrast, after 20 min of receptor engagement, the contacts were Lck‐independent. The relevance of the timing of inhibitor application provides a pharmacological concept for the maturation of T cell–substrate contacts.
Cobalt complexes with cinchonidine and quinidine: Effect of C8/C9 stereochemistry and 6′‐substitution on intermolecular interactions
Authors: Skórska Agnieszka , Stadnicka Katarzyna , Oleksyn Barbara J. 
Published: January 2005

AbstractThe title compounds, (cinchonidinium)trichlorocobalt(II) [(C19H23ON2)CoCl3] (CoCdn) and (quinidinium)trichlorocobalt(II) [(C20H25O2N2)CoCl3] (CoQd), are zwitterions that differ in absolute configuration and conformation. In both complexes, the sp3 nitrogen of quinuclidine is protonated, whereas the sp2 nitrogen of quinoline is linked to the Co(II) atom, which coordinates three chlorine atoms in distorted tetrahedral geometry. The mutual orientations of the quinoline and quinuclidine moieties in CoCdn and CoQd differ significantly because of different hydrogen bonding involving the hydroxyl group. In both complexes, the quinuclidine NH groups and hydroxyl groups are hydrogen‐bond donors to the chlorine atoms of Co(II) tetrahedra. In CoQd the hydrogen bonding leads to formation of a nine‐membered ring consisting of Co, two chlorines, and a fragment of the quinidine molecule. A comparison of the crystal structures of four Cinchona alkaloid complexes with trichlorocobalt(II) shows that their space groups are determined by the absolute configuration of the alkaloid, whereas the hydrogen‐bonding pattern is mainly affected by the substituent in the quinoline ring, i.e., by hydrogen or methoxyl group. Chirality 17:73–78, 2005. © 2005 Wiley‐Liss, Inc.
Pharmacologic implications of α‐adrenocreceptor interactive parameters for epinephrine enantiomers in the rat vas deferens
Authors: Rice Peter J. , Miller Duane D. , Sokoloski Theodore D. , Patil Popat N. 
Published: January 2005

AbstractAfter alkylation of a fraction of the total α‐adrenoreceptors by phenoxybenzamine in rat vas deferens, the dissociation constants of (−)‐ and (+)‐epinephrine in functional studies were 7 × 10−7 M and 2 × 10−5 M, respectively. In the adrenoreceptor‐containing tissue fraction, when 3H‐labeled WB4101 was used as the interacting ligand, for each enantiomer who affinity sites were found. Only the low‐affinity dissociation consant for each isomer correlates with the constant obtained from the functional studies. If the change in Gibb's free energy. ΔG°, is calculated from the low‐affinity binding constants, the values −8.1 and −6.2 kcal/mol for (−)‐ and (+)‐isomer, respectively, are obained. The small difference in the value between isomers forms a hydrogen bond with the receptor. The interaction of epinephrine with this receptor appears to be driven largely by the entropy of the drug‐receptor interaction with only a small nonsteroselective contribution from the enthalpy of ineraction.
Moleclar imprinting by noncovalent interactions: Tailor‐made chiral stationary phases of high selectivity and sample load capacity
Authors: Sellergren Börje 
Published: January 2005

AbstractA moleclar imprinting technique based on electrostatic and hydrogen bonding interactions was used to prepare polymers of high selectvity for the original print molecule (D or L form of an amino acid derivative). In the chromatographic mode ig enantioselectivity was observed, in particular for amino acid amides and basic amino acid esters. As indicated y he broad peaks obtained, the mass transfer, including the kinetics of the binding and dissociation process, was slow and appeared to be slower in systems where a higher number of interactions between the solute and the stationary phase could be expected. In such systems enhanced selectivity was observed. For polymers prepared at a lower temperature the mass transfer was more rapid and a higher selectivity was observed, wich allowed the separations to be performed at room temperature. A more rapid mass transfer and a higher selectivity could also be achieved by increasing the column temperature. Furthermore the polymers showed a high sample load capacity and a high stability, and the can easily be prepared.
Stereocontrolled synthesis of peptide bond isosteres
Authors: Whitesell James K. , Lawrence Robert M. 
Published: January 2005

AbstractAbsolute stereochemical control is employed in the synthesis of isosteres for dipeptide subunits 1; see Fig. (1) in which the amide linkage has been replaced by a trans carbon‐caron double bond. The synthesis affords access to the four stereoisomers of 1 in which R and R' = CH3, including the isostere of D‐alanine‐d‐alanine (D‐ala‐D‐Ala), 2.
Implications of chirality and geometric isomerism in some psychoactive drugs and their metabolites
Authors: Coutts R. T. , Baker G. B. 
Published: January 2005

AbstractMany drugs contain a chiral centre, or such a centre is introduced during metabolism of the drug in man and in animals. If a single chiral centre is present, the drug will normally exist as a mixture of two enantiomers, of which one may have quite different pharmacologic and/or toxic effects than the other. Chiral drugs that are used in psychiatry, and some other pharmacologically related drugs are identified, and the implications of the presence of one or two chiral centres in these drugs are discussed. Differences in pharmacologic properties of drug and metabolite enantiomers are identified and discussed. Also reviewed are the properties of some drugs used in psychiatry that both are chiral and display geometric isomerism.
Optical resolution of some biologically active compounds by chiral liquid chromatography on BSA‐silica (resolvosil) columns
Authors: Allenmark Stig , Andersson Shalini 
Published: January 2005

AbstractOptical resolution on the analytical scale of a number of racemic pharmaceuticals and some other biologically active compounds has been studied using immobilized bovine serum albumin (BSA) as the stationary phase. For some of the compounds the elution order was determined by the use of optically enriched fractions obtained from a preceding passage of a sample through a preparative column containing microcrystalline triacetylcellulose (MCTA). The reversal in the sign of optical rotation shown in the polarimetric elution profile from the latter, combined with the integrated peak area ratio obtained on resolution on the analytical column, gave directly the order of elution. For one of the benzothiadiazines studied (bendroflumethiazide), increasing the pH of the mobile phase produced opposite effects on the retention of the two enantiomers, leading to a large effect on the separation factor. For many of the compounds studied, high separation factors (α > 2) could be achieved.
Methiodide of the GABA antagonist (+)‐bicuculline is levorotatory
Authors: Simonyi Miklós , Blaskó Gábor , Kardos Julianna , Kajtár Márton 
Published: January 2005

AbstractThe appearance of positive charge on the nitrogen moiety of phthalideisoquinoline alkaloids brings about a strong change in the intensities of CD Cotton effects. Hence the optical rotations of enantiomeric salts and their parent base of identical configuration are often of opposite sign. Thus, the name (+)‐bicuculline‐methiodide for the methiodide salt of (+)‐bicuculline is false.
Direct chromatographic separation of 2‐arylpropionic acid enantiomers using tris(3,5‐dimethylphenylcarbamate)s of cellulose and amylose as chiral stationary phases
Authors: Okamoto Yoshio , Aburatani Ryo , Kaida Yuriko , Hatada Koichi , Inotsume Nobuo , Nakano Masahiro 
Published: January 2005

AbstractDirect optical resolution of antiinflammatory drugs such as ibuprofen, ketoprofen, flurbiprofen, and tiaprofenic acid were attempted by high‐performance liquid chromatography using tris(3,5‐dimethylphenylcarbamate)s of cellulose and amylose as chiral stationary phases. Although ibuprofen was not sufficiently resolved, the other three 2‐arylpropionic acids were completely resolved by amylose tris(3,5‐dimethylphenylcarbamate). Ibuprofen was resolved as anilide derivative.
Polarimetric detection in high‐performance liquid chromatography
Authors: Lloyd David K. , Goodall David M. 
Published: January 2005

AbstractChiroptical detection for HPLC is particularly useful as a selective detection method for chiral molecules, and in enantiomeric purity determination with partial chiral separation or without chiral separation. The recent development of laser‐based polarimeters with microdegree sensitivity has increased the applicability of optical rotation detection in HPLC. The detection limit of these instruments is submicrogram on‐column for many chiral compounds in analytical HPLC. A variety of applications of the selective detection of optically active molecules are reviewed. The use of polarimetric detection with partial chiral separation is considered, both as an aid to method development and for enantiomeric purity determination. Finally applications to enantiomeric purity determination without chiral separation are reviewed, with the dual use of nonchirally selective and chiroptical detectors to determine the total amount and optical purity of the analyte. Determinations of chiral purity for samples of high enantiomeric excess are described, which with laser‐based instrumentation may give accuracies of better than ± 1% with sample loadings of 50 μg on an achiral column. Applications to the study of enantioselective reactions are also considered, with determination of enantiomeric excess in near‐racemates to better than ± 0.1%.
Enantioselective aliphatic hydroxylations of racemic 1‐hydroxy‐3‐methylcholanthrene by rat liver microsomes
Authors: Shou Magang , Yang Shen K. 
Published: January 2005

AbstractEnantiomeric pairs of 1‐hydroxy‐3‐hydroxymethylcholanthrene (1‐OH‐3‐OHMC), 3‐methylcholanthrene (3MC) trans‐ and cis‐1,2‐diols, and 1‐hydroxy‐3‐methylcholanthrene (1‐OH‐3MC) were resolved by HPLC using a covalently bonded (R)‐N‐(3,5‐dinitrobenzoyl)phenylglycine chiral stationary phase (Pirkle type 1A) column. The absolute configuration of an enantiomeric 3MC trans‐1,2‐diol was established by the exciton chirality CD method following conversion to a bis‐p‐N,N‐dimethylaminobenzoate. Incubation of an enantiomeric 1‐OH‐3MC with rat liver microsomes resulted in the formation of enantiomeric 3MC trans‐ and cis‐1,2‐diols; the absolute configurations of the enantiomeric 1‐OH‐3MC and 3MC cis‐1,2‐diol were established on the basis of the absolute configuration of an enantiomeric 3MC trans‐1,2‐diol. Absolute configurations of enantiomeric 1‐OH‐3‐OHMC were determined by comparing their CD spectra with those of enantiomeric 1‐OH‐3MC. The relative amount of three aliphatic hydroxylation products formed by rat liver microsomal metabolism of racemic 1‐OH‐3MC was 1‐OH‐3‐OHMC > 3MC cis‐1,2‐diol > 3MC trans‐1,2‐diol. Enzymatic hydroxylation at C2 of racemic 1‐OH‐3MC was enantioselective toward the 1S‐enantiomer over the 1R‐enantiomer (∼3/1); hydroxylation at the C3‐methyl group was enantioselective toward the 1R‐enantiomer over the 1S‐enantiomer (∼58/42). Rat liver microsomal C2‐hydroxylation of racemic 1‐OH‐3MC resulted in a 3MC trans‐1,2‐diol with a (1S,2S)/(1R,2R) ratio of 63/37 and a 3MC cis‐1,2‐diol with a (1S,2R)/(1R,2S) ratio of 12/88, respectively.
Species differences in the generation of the chiral sulfoxide metabolite of albendazole in sheep and rats
Authors: Delatour P. , Benoit E. , Caude M. , Tambute A. 
Published: January 2005

AbstractThe prochiral anthelmintic drug albendazole was administered orally to sheep and rats. Blood samples were taken at standardized intervals during the time course of the plasma kinetics: 18 h in rats and 48 h in sheep. The enantiomeric ratio of the sulfoxide metabolite was determined by means of HPLC on a chiral stationary phase, the chiral selector of which was a N‐3,5‐dinitrobenzoyl derivative of (S)‐tyrosine. Two enantiomers were detected in both animal species but their ratios were inverted in rat vs. sheep. The evolution of the ratio is turned from a racemate at 15 min to 60(−):40(+) at 12 h in rats, while it moved from 23(−):77(+) at 3 h to 4(−):96(+) at 36 h after administration in sheep.