bluuebunny/crossref_metadata_2025_split huggingface dataset:
Exercise and dietary weight loss in overweight and obese older adults with knee osteoarthritis: The arthritis, diet, and activity promotion trial
Authors: Messier Stephen P. , Loeser Richard F. , Miller Gary D. , Morgan Timothy M. , Rejeski W. Jack , Sevick Mary Ann , Ettinger Walter H. , Pahor Marco , Williamson Jeff D. 
Published: May 2004

AbstractObjectiveThe Arthritis, Diet, and Activity Promotion Trial (ADAPT) was a randomized, single‐blind clinical trial lasting 18 months that was designed to determine whether long‐term exercise and dietary weight loss are more effective, either separately or in combination, than usual care in improving physical function, pain, and mobility in older overweight and obese adults with knee osteoarthritis (OA).MethodsThree hundred sixteen community‐dwelling overweight and obese adults ages 60 years and older, with a body mass index of ≥28 kg/m2, knee pain, radiographic evidence of knee OA, and self‐reported physical disability, were randomized into healthy lifestyle (control), diet only, exercise only, and diet plus exercise groups. The primary outcome was self‐reported physical function as measured with the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). Secondary outcomes included weight loss, 6‐minute walk distance, stair‐climb time, WOMAC pain and stiffness scores, and joint space width.ResultsOf the 316 randomized participants, 252 (80%) completed the study. Adherence was as follows: for healthy lifestyle, 73%; for diet only, 72%; for exercise only, 60%; and for diet plus exercise, 64%. In the diet plus exercise group, significant improvements in self‐reported physical function (P < 0.05), 6‐minute walk distance (P < 0.05), stair‐climb time (P < 0.05), and knee pain (P < 0.05) relative to the healthy lifestyle group were observed. In the exercise group, a significant improvement in the 6‐minute walk distance (P < 0.05) was observed. The diet‐only group was not significantly different from the healthy lifestyle group for any of the functional or mobility measures. The weight‐loss groups lost significantly (P < 0.05) more body weight (for diet, 4.9%; for diet plus exercise, 5.7%) than did the healthy lifestyle group (1.2%). Finally, changes in joint space width were not different between the groups.ConclusionThe combination of modest weight loss plus moderate exercise provides better overall improvements in self‐reported measures of function and pain and in performance measures of mobility in older overweight and obese adults with knee OA compared with either intervention alone.
Mechanical injury and psychosocial factors in the work place predict the onset of widespread body pain: A two‐year prospective study among cohorts of newly employed workers
Authors: Harkness Elaine F. , Macfarlane Gary J. , Nahit Elizabeth , Silman Alan J. , McBeth John 
Published: May 2004

AbstractObjectiveMechanical injury has been postulated as a risk factor for widespread pain, although to date, the evidence is weak. The aim of this study was to determine whether repeated exposure to mechanical trauma in the work place predicts the onset of widespread pain and to determine the relative contribution of mechanical trauma compared with psychosocial factors.MethodsIn this prospective cohort study of 1,081 newly employed subjects in 12 diverse occupational settings, we collected detailed information on mechanical exposure, posture, physical environment, and psychosocial risk factors in the work place. Study questionnaires were completed at baseline and at 12 and 24 months. Individuals free of widespread pain at baseline and 12 months were eligible for followup. Generalized estimating equations were used to determine which factors predicted the new onset of widespread pain.ResultsOf the 1,081 baseline respondents, 896 were free of widespread pain and were eligible for further study. Of these 896 subjects, 708 and 520 responded at 12 months and 24 months, respectively. The rates of new‐onset widespread pain were 15% at 12 months and 12% at 24 months. Several work place mechanical and posture exposures predicted the new onset of widespread pain: lifting >15 lbs with 1 hand, lifting >24 lbs with 2 hands, pulling >56 lbs, prolonged squatting, and prolonged working with hands at or above shoulder level. Of the psychosocial exposures, those who reported low job satisfaction, low social support, and monotonous work had an increased risk of new‐onset widespread pain. In multivariate analysis, monotonous work and low social support were found to be the strongest independent predictors of symptom onset.ConclusionOur findings demonstrate that the prevalence of new‐onset widespread pain was high, but among this young, newly employed work force, both physical and psychosocial factors played an important role.
Identification of mesenchymal progenitor cells in normal and osteoarthritic human articular cartilage
Authors: Alsalameh Saifeddin , Amin Rayya , Gemba Takefumi , Lotz Martin 
Published: May 2004

AbstractObjectiveTo determine the presence of mesenchymal progenitor cells (MPCs) in human articular cartilage.MethodsPrimary cell cultures established from normal and osteoarthritic (OA) human knee articular cartilage were analyzed for the expression of CD105 and CD166, cell surface markers whose coexpression defines mesenchymal stem cells (MSCs) in bone marrow and perichondrium. The potential of cartilage cells to differentiate to adipogenic, osteogenic, and chondrogenic lineages was analyzed after immunomagnetic selection for CD105+/CD166+ cells and was compared with bone marrow–derived MSCs (BM‐MSCs).ResultsUp to 95% of isolated cartilage cells were CD105+ and ∼5% were CD166+. The mean ± SEM percentage of CD105+/CD166+ cells in normal cartilage was 3.49 ± 1.93%. Primary cell cultures from OA cartilage contained significantly increased numbers of CD105+/CD166+ cells. Confocal microscopy confirmed the coexpression of both markers in the majority of BM‐MSCs and a subpopulation of cartilage cells. Differentiation to adipocytes occurred in cartilage‐derived cell cultures, as indicated by characteristic cell morphology and oil red O staining of lipid vacuoles. Osteogenesis was observed in isolated CD105+/CD166+ cells as well as in primary chondrocytes cultured in the presence of osteogenic supplements. Purified cartilage‐derived CD105+/CD166+ cells did not express markers of differentiated chondrocytes. However, the cells were capable of chondrocytic differentiation and formed cartilage tissue in micromass pellet cultures.ConclusionThese findings indicate that multipotential MPCs are present in adult human articular cartilage and that their frequency is increased in OA cartilage. This observation has implications for understanding the intrinsic repair capacity of articular cartilage and raises the possibility that these progenitor cells might be involved in the pathogenesis of arthritis.
Estimation in the continuous time mover‐stayer model with an application to bond ratings migration
Authors: Frydman Halina , Kadam Ashay 
Published: May 2004

AbstractThe usual tool for modelling bond ratings migration is a discrete, time‐homogeneous Markov chain. Such model assumes that all bonds are homogeneous with respect to their movement behaviour among rating categories and that the movement behaviour does not change over time. However, among recognized sources of heterogeneity in ratings migration is age of a bond (time elapsed since issuance). It has been observed that young bonds have a lower propensity to change ratings, and thus to default, than more seasoned bonds.The aim of this paper is to introduce a continuous, time‐non‐homogeneous model for bond ratings migration, which also incorporates a simple form of population heterogeneity. The specific form of heterogeneity postulated by the proposed model appears to be suitable for modelling the effect of age of a bond on its propensity to change ratings. This model, called a mover–stayer model, is an extension of a Markov chain.This paper derives the maximum likelihood estimators for the parameters of a continuous time mover–stayer model based on a sample of independent continuously monitored histories of the process, and develops the likelihood ratio statistic for discriminating between the Markov chain and the mover–stayer model. The methods are illustrated using a sample of rating histories of young corporate issuers. For these issuers the default probabilities predicted by the Markov chain and mover–stayer models are different. In particular for 1–4 years old bonds the mover–stayer model estimates substantially lower default probabilities from rating C than a Markov chain. Copyright © 2004 John Wiley & Sons, Ltd.
DM27, an enaminone, modifies the in vitro transport of antiviral therapeutic agents
Authors: Salama Noha N. , Scott Kenneth R. , Eddington Natalie D. 
Published: May 2004

AbstractObjective—For most antiviral drugs, low or variable bioavailability is attributed to poor absorption, susceptibility to efflux, or first pass metabolism. Enaminones are beta dicarbonyl compounds, which display P‐glycoprotein (P‐gp) substrate properties with high efflux ratios. This study investigates the influence of DM27, an enaminone, on the in vitro transport of antiviral agents and the possibility of using DM27 as a P‐gp inhibitor to prevent the efflux of certain antiretroviral agents.Methods—The transport of [3H]amprenavir, [3H]saquinavir, [3H]ritonavir, [14C]zidovudine (AZT) and [3H]acyclovir was evaluated across Caco‐2 cells with DM27 (10−10–10−4 M). In addition, the effect of DM27 (10−6 M) on the transport of transcellular and paracellular markers was tested to evaluate its influence on these transport pathways. The apparent permeability coefficient (Papp) for each drug or marker was calculated with/without DM27 and toxicity evaluation for DM27 was performed using the MTS assay.Results—The mean Papp for the investigated antiviral agents significantly increased by 22%–51% after DM27 incubation without any toxicity to the Caco‐2 cells. In addition, DM27 did not influence the transcellular or paracellular transport of propranolol and mannitol, respectively.Conclusions—DM27, an enaminone, increased the transport of antiretroviral drugs and acyclovir in a nontoxic manner without affecting the paracellular or transcellular transport of these drugs. This study suggests that DM27 may be used as a P‐gp efflux inhibitor to enhance the oral bioavailability of antiviral drugs and that drug–drug interactions will most probably be encountered upon co‐administration of P‐gp substrate drugs with enaminones. Copyright © 2004 John Wiley & Sons, Ltd.
β2‐amino acids—syntheses, occurrence in natural products, and components of β‐peptides1,2
Authors: Lelais Gérald , Seebach Dieter 
Published: May 2004

AbstractAlthough they are less abundant than their α‐analogues, β‐amino acids occur in nature both in free form and bound to peptides. Oligomers composed exclusively of β‐amino acids (so‐called β‐peptides) might be the most thoroughly investigated peptidomimetics. Beside the facts that they are stable to metabolism, exhibit slow microbial degradation, and are inherently stable to proteases and peptidases, they fold into well‐ordered secondary structures consisting of helices, turns, and sheets. In this respect, the most intriguing effects have been observed when β2‐amino acids are present in the β‐peptide backbone. This review gives an overview of the occurrence and importance of β2‐amino acids in nature, placing emphasis on the metabolic pathways of β‐aminoisobutyric acid (β‐Aib) and the appearance of β2‐amino acids as secondary metabolites or as components of more complex natural products, such as peptides, depsipeptides, lactones, and alkaloids. In addition, a compilation of the syntheses of both achiral and chiral β2‐amino acids is presented. While there are numerous routes to achiral β2‐amino acids, their EPC synthesis is currently the subject of many investigations. These include the diastereoselective alkylation and Mannich‐type reactions of cyclic‐ or acyclic β‐homoglycine derivatives containing chiral auxiliaries, the Curtius degradation, the employment of transition‐metal catalyzed reactions such as enantioselective hydrogenations, reductions, C–H insertions, and Michael‐type additions, and the resolution of rac. β2‐amino acids, as well as several miscellaneous methods. In the last part of the review, the importance of β2‐amino acids in the formation of β‐peptide secondary structures is discussed. © 2004 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 2004
Double Ring‐Closing Metathesis Reaction of Nitrogen‐Containing Tetraenes: Efficient Construction of Bicyclic Alkaloid Skeletons and Synthetic Application to Four Stereoisomers of Lupinine and Their Derivatives
Authors: Ma Shengming , Ni Bukuo 
Published: May 2004

AbstractThe double ring‐closing metathesis reaction of nitrogen‐containing tetraenes was studied. The selectivity of the fused/dumbbell‐type products can be controlled by the electronic/steric effects of the substituents attached to the CC bonds and the s‐cis/s‐trans conformational ratios of the substrates. This methodology has also been successfully applied to the enantioselective synthesis of four stereoisomers of lupinine and their derivatives.
How Does the Exchange of One Oxygen Atom with Sulfur Affect the Catalytic Cycle of Carbonic Anhydrase?
Authors: Schenk Stephan , Kesselmeier Jürgen , Anders Ernst 
Published: May 2004

AbstractWe have extended our investigations of the carbonic anhydrase (CA) cycle with the model system [(H3N)3ZnOH]+ and CO2 by studying further heterocumulenes and catalysts. We investigated the hydration of COS, an atmospheric trace gas. This reaction plays an important role in the global COS cycle since biological consumption, that is, uptake by higher plants, algae, lichens, and soil, represents the dominant terrestrial sink for this gas. In this context, CA has been identified by a member of our group as the key enzyme for the consumption of COS by conversion into CO2 and H2S. We investigated the hydration mechanism of COS by using density functional theory to elucidate the details of the catalytic cycle. Calculations were first performed for the uncatalyzed gas phase reaction. The rate‐determinig step for direct reaction of COS with H2O has an energy barrier of ΔG=53.2 kcal mol−1. We then employed the CA model system [(H3N)3ZnOH]+ (1) and studied the effect on the catalytic hydration mechanism of replacing an oxygen atom with sulfur. When COS enters the carbonic anhydrase cycle, the sulfur atom is incorporated into the catalyst to yield [(H3N)3ZnSH]+ (27) and CO2. The activation energy of the nucleophilic attack on COS, which is the rate‐determining step, is somewhat higher (20.1 kcal mol−1 in the gas phase) than that previously reported for CO2. The sulfur‐containing model 27 is also capable of catalyzing the reaction of CO2 to produce thiocarbonic acid. A larger barrier has to be overcome for the reaction of 27 with CO2 compared to that for the reaction of 1 with CO2. At a well‐defined stage of this cycle, a different reaction path can emerge: a water molecule helps to regenerate the original catalyst 1 from 27, a process accompanied by the formation of thiocarbonic acid. We finally demonstrate that nature selected a surprisingly elegant and efficient group of reactants, the [L3ZnOH]+/CO2/H2O system, that helps to overcome any deactivation of the ubiquitous enzyme CA in nature.
A Caged Lanthanide Complex as a Paramagnetic Shift Agent for Protein NMR
Authors: Prudêncio Miguel , Rohovec Jan , Peters Joop A. , Tocheva Elitza , Boulanger Martin J. , Murphy Michael E. P. , Hupkes Hermen‐Jan , Kosters Walter , Impagliazzo Antonietta , Ubbink Marcellus 
Published: May 2004

AbstractA lanthanide complex, named CLaNP (caged lanthanide NMR probe) has been developed for the characterisation of proteins by paramagnetic NMR spectroscopy. The probe consists of a lanthanide chelated by a derivative of DTPA (diethylenetriaminepentaacetic acid) with two thiol reactive functional groups. The CLaNP molecule is attached to a protein by two engineered, surface‐exposed, Cys residues in a bidentate manner. This drastically limits the dynamics of the metal relative to the protein and enables measurements of pseudocontact shifts. NMR spectroscopy experiments on a diamagnetic control and the crystal structure of the probe‐protein complex demonstrate that the protein structure is not affected by probe attachment. The probe is able to induce pseudocontact shifts to at least 40 Å from the metal and causes residual dipolar couplings due to alignment at a high magnetic field. The molecule exists in several isomeric forms with different paramagnetic tensors; this provides a fast way to obtain long‐range distance restraints.
Synthesis of Furano‐Epothilone D
Authors: Schinzer Dieter , Bourguet Erika , Ducki Sylvie 
Published: May 2004

AbstractThe total synthesis of furano‐epothilone D by a convergent route is reported. The key fragments are available on a large scale to provide sufficient material for biological evaluation. The approach involves a palladium‐catalyzed coupling that generates a highly functionalized aldehyde which is connected in a stereoselective aldol reaction to yield the framework of furano‐epothilone D. Finally, a macrolactonization provides furano‐epothilone D.
Correlation between Host–Guest Binding and Host Amplification in Simulated Dynamic Combinatorial Libraries
Authors: Corbett Peter T. , Otto Sijbren , Sanders Jeremy K. M. 
Published: May 2004

AbstractWe present a versatile computer model of diverse dynamic combinatorial libraries, and examine how molecular recognition between library members and a template can be used to amplify the best binders. The correlation between host–guest binding and amplification was examined for a set of 50 libraries with >300 components each over a wide range of template and building block concentrations. Depending on these concentrations correlations vary from poor (when using a large excess of template) to good (for very dilute libraries and/or substoichiometric template concentrations), highlighting the need to choose the experimental conditions for dynamic combinatorial libraries thoughtfully.
Long‐term efficacy and safety of zoledronic acid in the treatment of skeletal metastases in patients with nonsmall cell lung carcinoma and other solid tumors
Authors: Rosen Lee S. , Gordon David , Tchekmedyian N. Simon , Yanagihara Ronald , Hirsh Vera , Krzakowski Maciej , Pawlicki Marek , de Souza Paul , Zheng Ming , Urbanowitz Gladys , Reitsma Dirk , Seaman John ,   On behalf of the Zoledronic Acid Lung Cancer and Other Solid Tumors Study Group
Published: May 2004

AbstractBACKGROUNDThe authors previously reported the efficacy of a dose of 4 mg of zoledronic acid in reducing skeletal complications in patients with bone metastases secondary to lung carcinoma and other solid tumors (except carcinomas of the breast and prostate). In the current study, they update these results and report the long‐term efficacy and safety of 21 months of treatment with zoledronic acid in a randomized, placebo‐controlled trial.METHODSA total of 773 patients were randomized to receive zoledronic acid (4 mg or 8 mg) or placebo via a 15‐minute infusion every 3 weeks for 21 months. The 8‐mg dose later was reduced to 4 mg (8/4‐mg group). The primary efficacy endpoint was the percentage of patients at 21 months with ≥ 1 skeletal‐related event (SRE) (pathologic fracture, spinal cord compression, radiation therapy to bone, or surgery to bone). Secondary analyses (time to first SRE, annual incidence of SREs, and multiple‐event analysis) included hypercalcemia of malignancy.RESULTSFewer patients treated with zoledronic acid developed at least 1 SRE at 21 months compared with patients treated with placebo (39% of those treated at the 4‐mg dose [P =0.127] and 36% of those treated at the 8/4‐mg dose [P = 0.023], compared with 46% of those treated with placebo). Furthermore, 4 mg of zoledronic acid significantly delayed the median time to first SRE (236 days with 4 mg vs. 155 days with placebo; P = 0.009) and significantly reduced the annual incidence of SREs (1.74 per year with the 4‐mg dose vs. 2.71 per year with placebo; P = 0.012). Moreover, the 4‐mg dose of zoledronic acid was found to reduce the risk of developing a skeletal event by 31% (hazard ratio of 0.693; P = 0.003). Zoledronic acid was found to be well tolerated with long‐term use; the most commonly reported adverse events in all treatment groups included bone pain and the transient, acute‐phase reactions of nausea, anemia, and emesis.CONCLUSIONSTo the authors' knowledge, zoledronic acid is the first bisphosphonate to demonstrate long‐term safety and efficacy in this patient population. Cancer 2004. © 2004 American Cancer Society.
Interface Synthesis, Characterization and Catalytic Properties of Dialkyldichlorotin and Tetraalkyl Distannoxane Functionalities Grafted to Insoluble Polystyrene Beads by a Hexamethylene Spacer
Authors: Biesemans Monique , Mercier Frédéric A. G. , Van Poeck Manu , Martins José C. , Dumartin Gilles , Willem Rudolph 
Published: May 2004

AbstractInsoluble polystyrene‐grafted compounds of the type [(P−H)(1−t){P−(CH2)6SnBuCl2}t] and [(P−H)(1−t)({P−(CH2)6SnBuX}2O)t/2], where (P−H) represents a cross‐linked polystyrene, X is Cl, OH or OOCCH3, and t is the degree of functionalization, were synthesized from Amberlite XE‐305, a polystyrene cross‐linked with divinylbenzene. The compounds were characterized by elemental analysis, IR and Raman spectroscopy, solid‐state 13C and 117Sn NMR spectroscopy and, where appropriate, by 119Sn hr‐MAS NMR spectroscopy. The influence of the variable t and tin functionality on the catalytic activity of these compounds was assessed in the transesterification reaction of ethyl acetate with octanol. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)
Fluorescence Assay and Screening of Epoxide Opening by Nucleophiles
Authors: Badalassi Fabrizio , Klein Gérard , Crotti Paolo , Reymond Jean‐Louis 
Published: May 2004

AbstractTerminal epoxides such as 1 react with nucleophiles (H2O, Cl−, Br−, N3−, and CN−) at the primary oxirane carbon atom to give mostly anti‐Markovnikov‐type regioisomers 5a−d. The opening products of epoxide (R)‐1 with chloride (5a), bromide (5b) and azide (5c) are oxidized by horse liver alcohol dehydrogenase and NAD+ to give the corresponding ketones 7a−c and, subsequently, umbelliferone 4 by β‐elimination, leading to a fluorescence increase at λem = 460 ± 20 nm (λex = 360 ± 20 nm). The epoxide hydrolysis products give no signal. We used this enantio‐ and chemo‐selective fluorogenic assay for epoxide opening to search for catalytic antibodies for nucleophilic epoxide opening that were raised against 1,2‐azidoammonium hapten 8, as a mimic for epoxide opening by azide, and against chloromethyl phosphonate hapten 9, as a mimic for the transition state of chlorohydrin formation. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)