bluuebunny/crossref_metadata_2025_split huggingface dataset:
The genetic contribution to carpal tunnel syndrome in women: A twin study
Authors: Hakim Alan J. , Cherkas Lynn , El Zayat Sameh , MacGregor Alexander J. , Spector Tim D. 
Published: October 2002

AbstractObjectiveTo assess the relative genetic and environmental contribution to carpal tunnel syndrome (CTS) using a classic twin study of monozygotic (MZ) and dizygotic (DZ) twins.MethodsThe study group comprised unselected female twin pairs, between 20 and 80 years of age, from the St Thomas' UK Adult Twin Registry. Individuals completed a questionnaire that included details on potential risk factors for CTS. The diagnosis of CTS was made using a standardized hand pain diagram and validated criteria. The genetic contribution to CTS was assessed using variance component and regression methods, the heritability was adjusted for environmental confounders. The role of individual risk factors was assessed by a nested case‐control study.ResultsAn overall prevalence of 14.2% for CTS was found in a population of 4,488 females, comprising 867 MZ and 970 DZ twin pairs, and 814 singletons. The concordance for CTS was significantly higher in MZ compared with DZ twins (case‐wise concordance values of 0.35 and 0.24 respectively, with a significantly increased MZ:DZ ratio of 1.48; P = 0.03). Modeling produced a heritability estimate of 0.46 (95% CI 0.34–0.58) that was essentially unchanged after adjustment for environmental risk factors including age, body mass index, physical activities, and hormonal/reproductive factors. No major influence of any individual risk factor was seen in the case‐control analysis of 520 cases and 3,154 controls, apart from a modest association with menopausal status with an increased risk of 1.53 and 1.43 in the peri and postmenopausal groups. There was no overall effect of age or body mass index.ConclusionThis is the first study to explore the genetic component of CTS. Our data show that up to half of the liability to CTS in women is genetically determined, and this appears to be the single strongest risk factor, with only minor contributions from known environmental factors. Further studies should focus on genetic mechanisms that may lead to tests for susceptibility and detection of those at risk of developing CTS.
The enlarging clinical, genetic, and population spectrum of tumor necrosis factor receptor–associated periodic syndrome
Authors: Dodé Catherine , André Marc , Bienvenu Thierry , Hausfater Pierre , Pêcheux Christophe , Bienvenu Jacques , Lecron Jean‐Claude , Reinert Philippe , Cattan Daniel , Piette Jean‐Charles , Szajnert Marie‐France , Delpech Marc , Grateau Gilles ,   French Hereditary Recurrent Inflammatory Disorder Study Group
Published: October 2002

AbstractObjectiveTo characterize the frequency, clinical signs, and genotypic features of tumor necrosis factor receptor–associated periodic syndrome (TRAPS) in a series of 394 patients of various ethnic origins who have recurrent inflammatory syndromes.MethodsSequencing of the coding region of the TNFRSF1A gene was performed in 128 patients in whom there was a high suspicion of TRAPS, and denatured high‐performance liquid chromatography was used to systematically screen for TNFRSF1A in 266 patients with recurrent inflammatory syndrome and no or only 1 Mediterranean fever gene (MEFV) mutation.ResultsTNFRSF1A mutations were found in 28 (7.1%) of 394 unrelated patients. Nine (32%) of the 28 patients had a family history of recurrent inflammatory syndromes. In 13 patients, the length of the attack of inflammation was fewer than 5 days. Three of the mutations (Y20H, L67P, and C96Y) were novel. Two mutations, R92Q and (mainly) P46L, found in 12 and 10 patients, respectively, had lower penetrance compared with other mutations. TNFRSF1A mutations were found in patients of various ethnic origins, including those at risk for familial Mediterranean fever (FMF): Armenians, Sephardic Jews, and especially Arabs from Maghreb. Only 3 (10.7%) of the 28 patients had amyloidosis.ConclusionTRAPS is an underdiagnosed cause of recurrent inflammatory syndrome. Its presence in the population of persons of Mediterranean ancestry and the short duration of the attacks of inflammation can lead to a fallacious diagnosis of FMF. Because an accurate diagnosis in patients with recurrent inflammatory syndromes is crucial for proper clinical management and treatment, genetic screening for TNFRSF1A is warranted.
Factors of importance for work disability in women with fibromyalgia: An interview study
Authors: Liedberg Gunilla M. , Henriksson Chris M. 
Published: October 2002

AbstractObjectiveFibromyalgia symptoms such as continuous pain, tiredness, hyperalgesia, and allodynia limit gainful employment. The present study examines which factors influence the decision to remain in a work role for women with fibromyalgia. This information is important for the individual and for public finances.MethodsQualitative interviews were performed with 39 women, 19 of whom were gainfully employed and 20 who had stopped working. The transcribed interviews were analyzed and divided into categories and subcategories.ResultsFour categories appear, at societal and individual levels, that were regarded as important by the women for remaining in a work role.ConclusionsThe ability to remain at work depends not only on limitations in work capacity, but also on the capacity of society to adjust work environments and work tasks. More individual solutions are needed to allow women with fibromyalgia to maintain work roles.
Immunosuppressive therapy in lupus nephritis: The Euro‐Lupus Nephritis Trial, a randomized trial of low‐dose versus high‐dose intravenous cyclophosphamide
Authors: Houssiau Frédéric A. , Vasconcelos Carlos , D'Cruz David , Sebastiani Gian Domenico , Garrido Enrique de Ramon , Danieli Maria Giovanna , Abramovicz Daniel , Blockmans Daniel , Mathieu Alessandro , Direskeneli Haner , Galeazzi Mauro , Gül Ahmet , Levy Yair , Petera Peter , Popovic Rajko , Petrovic Radmila , Sinico Renato Alberto , Cattaneo Roberto , Font Josep , Depresseux Geneviève , Cosyns Jean‐Pierre , Cervera Ricard 
Published: October 2002

AbstractObjectiveGlomerulonephritis is a severe manifestation of systemic lupus erythematosus (SLE) that is usually treated with an extended course of intravenous (IV) cyclophosphamide (CYC). Given the side effects of this regimen, we evaluated the efficacy and the toxicity of a course of low‐dose IV CYC prescribed as a remission‐inducing treatment, followed by azathioprine (AZA) as a remission‐maintaining treatment.MethodsIn this multicenter, prospective clinical trial (the Euro‐Lupus Nephritis Trial [ELNT]), we randomly assigned 90 SLE patients with proliferative glomerulonephritis to a high‐dose IV CYC regimen (6 monthly pulses and 2 quarterly pulses; doses increased according to the white blood cell count nadir) or a low‐dose IV CYC regimen (6 fortnightly pulses at a fixed dose of 500 mg), each of which was followed by AZA. Intent‐to‐treat analyses were performed.ResultsFollowup continued for a median of 41.3 months in the low‐dose group and 41 months in the high‐dose group. Sixteen percent of those in the low‐dose group and 20% of those in the high‐dose group experienced treatment failure (not statistically significant by Kaplan‐Meier analysis). Levels of serum creatinine, albumin, C3, 24‐hour urinary protein, and the disease activity scores significantly improved in both groups during the first year of followup. Renal remission was achieved in 71% of the low‐dose group and 54% of the high‐dose group (not statistically significant). Renal flares were noted in 27% of the low‐dose group and 29% of the high‐dose group. Although episodes of severe infection were more than twice as frequent in the high‐dose group, the difference was not statistically significant.ConclusionThe data from the ELNT indicate that in European SLE patients with proliferative lupus nephritis, a remission‐inducing regimen of low‐dose IV CYC (cumulative dose 3 gm) followed by AZA achieves clinical results comparable to those obtained with a high‐dose regimen.
Patient preferences for treatment of lupus nephritis
Authors: Fraenkel Liana , Bogardus Sidney , Concato John 
Published: October 2002

AbstractObjectiveTo examine the amount of improvement in renal survival that lupus patients require before choosing cyclophosphamide over azathioprine for the treatment of lupus nephritis.MethodsPatients were presented with descriptions of cyclophosphamide and azathioprine and asked to indicate their preferred choice if each conferred an equal probability of renal survival. Strength of preference was assessed by systematically increasing the probability of renal survival of the more toxic treatment until the respondent's choice switched.ResultsNinety‐three well‐educated women (mean age ± SD 40 ± 7 years) participated in the study. Ninety‐eight percent (91/93) of the participants chose azathioprine over cyclophosphamide when both drugs conferred an equal probability of renal survival. Although most subjects switched preferences to cyclophosphamide for better renal survival, 31% (28/91) were unwilling to switch from azathioprine to cyclophosphamide for improved short‐term renal survival, and 15% (14/91) were unwilling to switch from azathioprine to cyclophosphamide for improved long‐term renal survival.ConclusionAlthough the majority of patients switched preferences to cyclophosphamide for better renal survival, a substantial minority was unwilling to accept the toxicity associated with cyclophosphamide, even if it was much better than azathioprine at preventing renal failure.
Information‐seeking and mediated searching. Part 1. Theoretical framework and research design
Authors: Spink Amanda , Wilson T.D. , Ford Nigel , Foster Allen , Ellis David 
Published: October 2002

AbstractOur project has investigated the processes of mediated information retrieval (IR) searching during human information‐seeking processes to characterize aspects of this process, including information seekers' changing situational contexts; information problems; uncertainty reduction; successive searching, cognitive styles; and cognitive and affective states. The research has involved observational, longitudinal data collection in the United States and United Kingdom. Three questionnaires were used for pre‐ and postsearch interviews: reference interview, information seeker postsearch, and search intermediary postsearch questionnaires. In addition, the Sheffield team employed a fourth set of instruments in a follow‐up interview some 2 months after the search. A total of 198 information seekers participated in a mediated on‐line search with a professional intermediary using the Dialog Information Service. Each mediated search process was audio taped and search transaction log recorded. The findings are presented in four parts. Part I presents the background, theoretical framework, models, and research design used during the research. Part II is devoted to exploring changes in information seekers' uncertainty during the mediated process. Part III provides results related to successive searching. Part IV reports findings related to cognitive styles, individual differences, age and gender. Additional articles that discuss further findings from this complex research project, including: (1) an integrated model of information seeking and searching, (2) assessment of mediated searching, and (3) intermediary‐information seeker communication, are in preparation and will be published separately.
Information seeking and mediated searching study. Part 3. Successive searching
Authors: Spink Amanda , Wilson T.D. , Ford Nigel , Foster Allen , Ellis David 
Published: October 2002

AbstractOur project has investigated the processes of mediated information retrieval (IR) searching during human information‐seeking processes to characterize aspects of this process, including information seekers' changing situational contexts; information problems; uncertainty reduction; successive searching, cognitive styles; and cognitive and affective states. The research has involved observational, longitudinal data collection in the United States and the United Kingdom. Three questionnaires were used for pre‐ and postsearch interviews: reference interview, information‐seeker postsearch, and search intermediary postsearch questionnaires. In addition, the Sheffield team employed a fourth set of instruments in a follow‐up interview some 2 months after the search. A total of 198 information seekers participated in a mediated on‐line search with a professional intermediary using the Dialog Information Service. Each mediated search process was audiotaped and search transaction logs recorded. The findings are presented in four parts. Part I presents the background, theoretical framework, models, and research design used during the research. Part II is devoted to exploring changes in information seekers' uncertainty during the mediated process. Part III provides results related to successive searching. Part IV reports findings related to cognitive styles, individual differences, age and gender. Additional articles that discuss further findings from this complex research project, including: (1) an integrated model of information seeking and searching, (2) assessment of mediated searching, and (3) intermediary information‐seeker communication, are in preparation and will be published separately.
An investigation of the influence of indexing exhaustivity and term distributions on a document space
Authors: Wolfram Dietmar , Zhang Jin 
Published: October 2002

AbstractThe authors investigate the influence of index term distributions, and indexing exhaustivity levels on the document space within a visual information retrieval environment called DARE. Using combinations of three levels of term distributions (shallow, observed, steep) and indexing exhaustivity (low, observed, high), hypothetical document sets were generated and projected onto the DARE environment. The results from the simulated document sets demonstrate the importance of term distribution and exhaustivity characteristics on the density of document spaces and their implications for retrieval, particularly when different term weighting schemes are used. The results also demonstrate how different combinations of exhaustivity and term distributions may result in similar document space density characteristics.
Evaluation of SupermixTM as an in vitro model of human liver microsomal drug metabolism
Authors: Venkatakrishnan Karthik , von Moltke Lisa L. , Greenblatt David J. 
Published: October 2002

AbstractSUPERMIXTM is a commercially available formulation of insect cell‐expressed human drug‐metabolizing cytochrome P450 (CYP) isoforms, mixed in proportions that are optimized to parallel their relative activities in human liver microsomes. We have evaluated the apparent functional affinity and capacity of individual CYP isoforms in SUPERMIXTM in comparison with microsomes from a panel of 12 human livers, using enzyme kinetic studies of isoform‐selective index reactions. In addition, we have measured the concentration of NADPH cytochrome P450 oxidoreductase (OR) in SUPERMIXTM and compared it with the concentrations of this accessory electron transfer protein in human liver microsomes. No important differences were evident in the catalytic activities of CYPs 1A2, 2C8, 2C9, 2C19, 2D6 and 3A4 between SUPERMIXTM and human liver microsomes. However, SUPERMIXTM lacks CYP2B6 activity and did not hydroxylate the antidepressant bupropion, a clinically relevant substrate of this enzyme. In addition, the concentration of OR in SUPERMIXTM (1198 pmol mg protein−1) is 17‐fold higher than the mean value in human liver microsomes (70 pmol mg protein−1). In conclusion, SUPERMIXTM lacks CYP2B6 activity and contains supraphysiological concentrations of the accessory electron transfer protein OR. These factors should be considered when this formulation is used as an in vitro model in human liver microsomal drug metabolism studies. Copyright © 2002 John Wiley & Sons, Ltd.
The folic acid biosynthesis pathway in bacteria: evaluation of potential for antibacterial drug discovery
Authors: Bermingham Alun , Derrick Jeremy P. 
Published: October 2002

AbstractThe potential of the folic acid biosynthesis pathway as a target for the development of antibiotics has been acknowledged for many years and validated by the clinical use of several drugs. Recently, the crystal structures of all but one of the enzymes in the pathway from GTP to dihydrofolate have been determined. Given that structure‐based drug design strategies are now widely employed, these recent developments have prompted a re‐evaluation of the potential of each of the enzymes in the pathway as a target for development of specific inhibitors. Here, we review the current knowledge of the structure and mechanism of each enzyme in the bacterial folic acid biosynthesis pathway from GTP to dihydrofolate and draw conclusions regarding the potential of each enzyme as a target for therapeutic intervention. BioEssays 24:637–648, 2002. © 2002 Wiley Periodicals, Inc.
Going malignant: the hypoxia‐cancer connection in the prostate
Authors: Hochachka P.W. , Rupert J.L. , Goldenberg L. , Gleave M. , Kozlowski P. 
Published: October 2002

AbstractThe metabolic organization of both normal and malignant prostate cellular phenotypes involves some unusual and surprising features. In particular, both conditions exhibit ratios of NADH/NAD+ and NADPH/NADP+ charactersitic of high oxidative states despite a chronic shortage of O2 in both conditions. In this paper, we observe that, in prostate cancer cells, the oxidizing power of the fatty acid synthesis (FAS) pathway is so large that redox is stabilized more favorably (more oxidized) than in normal prostate cells. This FAS‐facilitated redox improvement occurs despite the fact that malignant cells are more O2 limited and therefore express more hypoxia inducible factor 1 (HIF1) and express hypoxia‐regulated genes more robustly. This unusual metabolic situation clearly separates direct regulatory effects of redox balance from secondary effects of hypoxia per se. The physiological significance of the FAS pathway is thus the harnessing of its oxidizing power for improving redox balance despite conditions of more extreme hypoxia. Similar hypoxia defense strategies are found in animal species that are unusually tolerant to oxygen lack. Our hypothesis is that the metabolic organization in the “low zinc, low citrate” phenotype reflects an hypoxia‐defense adaptation geared toward redox balance, with prostate cancer cells being relatively more oxidized, even if more hypoxic, than normal prostate cells. Recognition and understanding of these redox balancing and hypoxia defense functions may lead to new intervention strategies by developing new intracellular targets for prostate cancer therapy. BioEssays 24:749–757, 2002. © 2002 Wiley Periodicals, Inc.
Hydration of biological molecules: Lipids versus nucleic acids
Authors: Pohle W. , Gauger D. R. , Dornberger U. , Birch‐Hirschfeld E. , Selle C. , Rupprecht A. , Bohl M. 
Published: October 2002

AbstractWe used FTIR spectroscopy to comparatively study the hydration of films prepared from nucleic acids (DNA and double‐stranded RNA) and lipids (phosphatidylcholines and phosphatidylethanolamines chosen as the most abundant ones) at room temperature by varying the ambient relative humidity in terms of solvent‐induced structural changes. The nucleic acids and phospholipids both display examples of polymorphism on the one hand and structural conservatism on the other; even closely related representatives behave differently in this respect. DNA undergoes a hydration‐driven A–B conformational transition, but RNA maintains an A‐like structure independently of the water activity. Similarly, a main transition between the solid and liquid‐crystalline phases can be induced lyotropically in certain phosphatidylcholines, while their phosphatidylethanolamine counterparts do not exhibit chain melting under the same conditions. A principal difference concerning the structural changes that occur in the studied biomolecules is given by the relevant water–substrate stoichiometries. These are rather high in DNA and often low in phospholipids, suggesting different mechanisms of action of the hydration water that appears to induce structural changes on global‐ and local‐mode levels, respectively. © 2002 Wiley Periodicals, Inc. Biopolymers (Biospectroscopy) 67: 499–503, 2002
Study of high molecular weight wheat glutenin subunit 1Dx5 by 13C and 1H solid‐state NMR spectroscopy. I. Role of covalent crosslinking
Authors: Alberti Enrica , Gilbert Simon M. , Tatham Arthur S. , Shewry Peter R. , Gil Ana M. 
Published: October 2002

AbstractThis work describes a carbon and proton solid‐state NMR study of the hydration of a high molecular weight wheat glutenin subunit, 1Dx5. The effect of the presence of disulfide bonds on the hydration behavior of the subunit is investigated by a comparison of the unalkylated and alkylated forms of the protein. Hydration induces partial plasticization of the protein so that some segments become more mobile than others. The 13C cross‐polarization and magic‐angle spinning (MAS) spectra of the samples in the dry state and at two hydration levels (∼40 and ∼65% D2O) were used to monitor the protein fraction resisting plasticization (trains). Conversely, 13C single pulse excitation and 1H‐MAS experiments were used to gain information on the more plasticized segments (loops). The molecular motion of the two protein dynamic populations was further characterized by 13C T1 and 1H T1ρ, T2, and T1 relaxation times. The results suggest that hydration leads to the formation of a network held by a cooperative action of hydrogen bonded glutamines and some hydrophobic interactions. The looser protein segments are suggested to be glycine‐ and glutamine‐rich segments. The primary structure is therefore expected to significantly determine the proportion of trains and loops in the network. The presence of disulfide bonds was observed to promote easier plasticization of the protein and the formation of a more mobile network, probably involving a higher number of loops and/or larger loops. © 2002 Wiley Periodicals, Inc. Biopolymers (Biospectroscopy) 67: 487–498, 2002
Determination of α‐helix and β‐sheet stability in the solid state: A solid‐state NMR investigation of poly(L‐alanine)
Authors: Henzler Wildman Katherine A. , Lee Dong‐Kuk , Ramamoorthy A. 
Published: October 2002

AbstractThe relative stability of α‐helix and β‐sheet secondary structure in the solid state was investigated using poly(L‐alanine) (PLA) as a model system. Protein folding and stability has been well studied in solution, but little is known about solid‐state environments, such as the core of a folded protein, where peptide packing interactions are the dominant factor in determining structural stability. 13C cross‐polarization with magic angle spinning (CPMAS) NMR spectroscopy was used to determine the backbone conformation of solid powder samples of 15‐kDa and 21.4‐kDa PLA before and after various sample treatments. Reprecipitation from helix‐inducing solvents traps the α‐helical conformation of PLA, although the method of reprecipitation also affects the conformational distribution. Grinding converts the secondary structure of PLA to a final steady‐state mixture of 55% β‐sheet and 45% α‐helix at room temperature regardless of the initial secondary structure. Grinding PLA at liquid nitrogen temperatures leads to a similar steady‐state mixture with 60% β‐sheet and 40% α‐helix, indicating that mechanical shear force is sufficient to induce secondary structure interconversion. Cooling the sample in liquid nitrogen or subjecting it to high pressure has no effect on secondary structure. Heating the sample without grinding results in equilibration of secondary structure to 50% α‐helix/50% β‐sheet at 100°C when starting from a mostly α‐helical state. No change was observed upon heating a β‐sheet sample, perhaps due to kinetic effects and the different heating rate used in the experiments. These results are consistent with β‐sheet approximately 260 J/mol more stable than α‐helix in solid‐state PLA. © 2002 Wiley Periodicals, Inc. Biopolymers 64: 246–254, 2002