bluuebunny/crossref_metadata_2025_split huggingface dataset:
Early response to immunosuppressive therapy predicts good renal outcome in lupus nephritis: Lessons from long‐term followup of patients in the Euro‐Lupus Nephritis Trial
Authors: Houssiau Frédéric A. , Vasconcelos Carlos , D'Cruz David , Sebastiani Gian Domenico , de Ramon Garrido Enrique , 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: December 2004

AbstractObjectiveIn the Euro‐Lupus Nephritis Trial (ELNT), 90 patients with lupus nephritis were randomly assigned to a high‐dose intravenous cyclophosphamide (IV CYC) regimen (6 monthly pulses and 2 quarterly pulses with escalating doses) or a low‐dose IV CYC regimen (6 pulses of 500 mg given at intervals of 2 weeks), each of which was followed by azathioprine (AZA). After a median followup of 41 months, a difference in efficacy between the 2 regimens was not observed. The present analysis was undertaken to extend the followup and to identify prognostic factors.MethodsRenal function was prospectively assessed quarterly in all 90 patients except 5 who were lost to followup. Survival curves were derived using the Kaplan‐Meier method.ResultsAfter a median followup of 73 months, there was no significant difference in the cumulative probability of end‐stage renal disease or doubling of the serum creatinine level in patients who received the low‐dose IV CYC regimen versus those who received the high‐dose regimen. At long‐term followup, 18 patients (8 receiving low‐dose and 10 receiving high‐dose treatment) had developed permanent renal impairment and were classified as having poor long‐term renal outcome. We demonstrated by multivariate analysis that early response to therapy at 6 months (defined as a decrease in serum creatinine level and proteinuria <1 gm/24 hours) was the best predictor of good long‐term renal outcome.ConclusionLong‐term followup of patients from the ELNT confirms that, in lupus nephritis, a remission‐inducing regimen of low‐dose IV CYC followed by AZA achieves clinical results comparable with those obtained with a high‐dose regimen. Early response to therapy is predictive of good long‐term renal outcome.
Evidence for a novel rheumatoid arthritis susceptibility locus on chromosome 6p
Authors: Brintnell William , Zeggini Eleftheria , Barton Anne , Thomson Wendy , Eyre Stephen , Hinks Anne , Silman Alan J. , Worthington Jane 
Published: December 2004

AbstractObjectiveTo investigate whether the large linkage peak on chromosome 6p harbors rheumatoid arthritis (RA) susceptibility loci in addition to the well‐characterized HLA–DRB1 gene.MethodsDNA samples obtained from 377 UK RA affected sibling pair (ASP) families, comprising test (181 ASPs) and replication (196 ASPs) cohorts, were used for linkage analysis. Three hundred eighty‐four patients with RA derived from a subset of 192 ASPs were compared with a panel of 288 unrelated healthy controls for association studies. Samples were genotyped for 35 microsatellites and 25 single‐nucleotide polymorphisms (SNPs).ResultsIn the test cohort, the maximum logarithm of odds (LOD) score was obtained over D6S1260 (LOD 7.1). Evidence for linkage to the telomeric portion of the peak was increased in subsets of ASPs in which both individuals had erosive disease or both carried 2 copies of the shared epitope. HLA–A, HLA–DRB1, and 8 additional markers showed evidence of linkage in the presence of association with RA (using the extended transmission disequilibrium test [ETDT]). The positive ETDT result for 2 adjacent markers (D6S1665 and 210901‐4) mapping to the telomeric end of the linked region (∼11 Mb from DRB1) was replicated (for D6S1665) in the second cohort of ASPs. Haplotypic overtransmission of pairwise combinations between D6S1665*7 and 210901‐4*4 was identified through the TDTPhase program. Multipoint conditional analysis showed this effect to be independent of HLA–DRB1. SNP‐based association studies of the region identified a 4‐marker haplotype in the DEK gene that was significantly associated with RA (P = 0.009).ConclusionEvidence has been presented for an RA susceptibility locus mapping under the linkage peak on 6p, 11 Mb telomeric of HLA–DRB1. Preliminary association data implicate the gene DEK.
Association of severe vertebral fractures with reduced quality of life: Reduction in the incidence of severe vertebral fractures by teriparatide
Authors: Crans G. G. , Silverman S. L. , Genant H. K. , Glass E. V. , Krege J. H. 
Published: December 2004

AbstractObjectiveThe association between vertebral fracture severity and health‐related quality of life (HRQOL) was investigated in a subset of patients in the Fracture Prevention Trial. We sought to determine whether vertebral fracture severity was associated with HRQOL scores, and if so, to determine the effects of teriparatide (recombinant human parathyroid hormone 1‐34) on vertebral fracture grades that most strongly impact HRQOL in postmenopausal women with osteoporosis.MethodsVertebral fracture severity was assessed by the visual semiquantitative (SQ) method. A subset of 444 patients with a baseline radiograph completed the Osteoporosis Assessment Questionnaire. Baseline HRQOL scores were modeled as a function of maximum baseline vertebral fracture grade, while controlling for age, bone mineral density, body mass index, and back pain.ResultsThe effect of baseline vertebral fracture grade on baseline HRQOL was statistically significant, while interactions between vertebral fracture grade and the other variables were not statistically significant. SQ grade 3 (SQ3) vertebral fractures were associated with a significantly lower overall HRQOL score and with significantly lower physical function, symptoms, and emotional status dimension scores. After a median of 19 months of therapy, new or worsening SQ3 vertebral fractures occurred in 21 of 448 patients (4.7%) in the placebo group compared with 3 of 444 patients (0.7%) in the 20 μg/day teriparatide group. The risk of developing a new or worsened SQ3 vertebral fracture was reduced by 86% (P < 0.001) in patients treated with 20 μg/day teriparatide.ConclusionCompared with prevalent fractures of lesser severity, SQ3 vertebral fractures were associated with reduced HRQOL. Teriparatide treatment significantly reduced the risk of new or worsening SQ3 vertebral fractures. These findings suggest, but do not directly demonstrate, a benefit of teriparatide on HRQOL.
Association of a functional CD19 polymorphism with susceptibility to systemic sclerosis
Authors: Tsuchiya Naoyuki , Kuroki Kimiko , Fujimoto Manabu , Murakami Yoshinori , Tedder Thomas F. , Tokunaga Katsushi , Takehara Kazuhiko , Sato Shinichi 
Published: December 2004

AbstractObjectiveCD19 is overexpressed in B cells from patients with systemic sclerosis (SSc), and plays a crucial role not only for autoantibody production, but also for skin fibrosis in mouse models. We previously reported the association of a GT repeat polymorphism in the 3′‐untranslated region (3′‐UTR) of CD19 with human systemic lupus erythematosus. In this study, we examined whether CD19 polymorphisms are associated with genetic susceptibility to SSc.MethodsA case–control association study was performed for CD19 polymorphisms, −499G>T in the promoter region and a GT repeat polymorphism in the 3′‐UTR, in 134 patients with SSc and 96 healthy individuals recruited at Kanazawa University. CD19 expression levels in the peripheral blood naive and memory B cells from SSc patients were examined by 2‐color flow cytometry.ResultsCarrier frequencies of the −499T allele in the promoter (odds ratio [OR] 2.18, 95% confidence interval [95% CI] 1.31–3.86, P = 0.003) and of the (GT)14 allele in the 3′‐UTR (OR 1.86, 95% CI 1.05–3.28, P = 0.03) were significantly increased in SSc patients compared with healthy controls. Association was particularly evident in patients with limited cutaneous SSc with anticentromere antibodies. These alleles were in linkage disequilibrium, but the −499T allele seemed to play a primary role. CD19 expression levels in peripheral blood B cells were significantly elevated in both naive (P = 0.0029) and memory (P = 0.0022) B cells from patients with SSc who had the −499T allele as compared with those without the −499T allele.ConclusionThe CD19 −499G>T polymorphism is associated with higher CD19 expression in B cells, and with susceptibility to SSc.
NF‐κB–regulated expression of cellular FLIP protects rheumatoid arthritis synovial fibroblasts from tumor necrosis factor α–mediated apoptosis
Authors: Bai Shaochun , Liu Hongtao , Chen Kun‐Hung , Eksarko Polikseni , Perlman Harris , Moore Terry L. , Pope Richard M. 
Published: December 2004

AbstractObjectiveLittle apoptosis has been observed in rheumatoid arthritis (RA) synovial tissues. Tumor necrosis factor α (TNFα) is expressed in the joints of patients with RA, yet RA synovial fibroblasts are relatively resistant to apoptosis induced by TNFα. Recently, we demonstrated that FLIP is highly expressed in the RA joint. These studies were performed to determine if TNFα‐induced NF‐κB controls the expression of FLIP long (FLIPL) and FLIP short (FLIPS) in RA synovial fibroblasts and to determine the role of FLIP in the control of TNFα‐induced apoptosis.MethodsRA synovial fibroblasts were isolated from RA synovial tissues and used between passages 3 and 9. RA synovial or control fibroblasts were sham infected or infected with a control adenovirus vector or one expressing the super‐repressor IκBα (srIκBα). The cells were stimulated with TNFα or a control vehicle, and expression of FLIPL and FLIPS was determined by isoform‐specific real‐time polymerase chain reaction and Western blot analysis. Cell viability was determined by XTT cleavage, and apoptosis was determined by annexin V staining, DNA fragmentation, and activation of caspases 8 and 3.ResultsTNFα induced the expression of both isoforms of FLIP messenger RNA (mRNA) in RA synovial fibroblasts; however, FLIPL was the dominant isoform detected by Western blot analysis. In control fibroblasts, TNFα induced the expression of FLIPL and FLIPS mRNA and protein. The TNFα‐induced, but not the basal, expression of FLIP was regulated by NF‐κB. When NF‐κB activation was suppressed by the expression of srIκBα, TNFα‐mediated apoptosis was induced. TNFα‐induced apoptotic cell death was mediated by caspase 8 activation and was prevented by the ectopic expression of FLIPL or the caspase 8 inhibitor CrmA.ConclusionThe TNFα‐induced, but not the basal, expression of FLIP is regulated by NF‐κB in RA synovial fibroblasts. The resistance of RA synovial fibroblasts to TNFα‐induced apoptosis is mediated by the NF‐κB–regulated expression of FLIP. These observations support the role of NF‐κB and FLIP as attractive therapeutic targets in RA.
Use of mass spectrometry to identify protein biomarkers of disease severity in the synovial fluid and serum of patients with rheumatoid arthritis
Authors: Liao Hua , Wu Jiang , Kuhn Eric , Chin Wendy , Chang Betty , Jones Michael D. , O'Neil Steve , Clauser Karl R. , Karl Johann , Hasler Fritz , Roubenoff Ronenn , Zolg Werner , Guild Brad C. 
Published: December 2004

AbstractObjectiveTo identify a panel of candidate protein biomarkers of rheumatoid arthritis (RA) that can predict which patients will develop erosive, disabling disease.MethodsA 2‐step proteomic approach was used for biomarker discovery and verification. In the first step, 2‐dimensional liquid chromatography–coupled tandem mass spectrometry was used to generate protein profiles of synovial fluid (SF) from patients with either erosive RA (n = 5) or nonerosive RA (n = 5). In the second step, the selected candidate markers were verified using quantitative multiple reaction monitoring mass spectrometry in sera of patients with erosive RA (n = 15) or nonerosive RA (n = 15) and of healthy controls (n = 15).ResultsThrough differential profiling of proteins in the <40‐kd portion of the SF proteome, we selected 33 prospective candidate biomarkers from a total of 418 identified proteins. Among the proteins that were elevated in the SF of patients with erosive RA were C‐reactive protein (CRP) and 6 members of the S100 protein family of calcium‐binding proteins. Significantly, levels of CRP, S100A8 (calgranulin A), S100A9 (calgranulin B), and S100A12 (calgranulin C) proteins were also elevated in the serum of patients with erosive disease compared with patients with nonerosive RA or healthy individuals.ConclusionSeveral potential protein marker candidates have been identified for prognosis of the erosive form of RA. This study demonstrates the facility of using protein mass spectrometry in SF and serum for global discovery and verification of clinically relevant sets of disease biomarkers.
Revised versions of the Childhood Health Assessment Questionnaire (CHAQ) are more sensitive and suffer less from a ceiling effect
Authors: Lam Catherine , Young Nancy , Marwaha Jasvir , McLimont Marjorie , Feldman Brian M. 
Published: December 2004

AbstractObjectiveTo determine the relative discriminant validity of 3 new versions of the Childhood Health Assessment Questionnaire (CHAQ) and to determine the relative concordance between children and their parents.MethodsThe parents of 48 children with musculoskeletal disability and 101 nondisabled controls were given the CHAQ and the 3 revised versions in random order. Children older than 5 years also completed the questionnaires.ResultsAll 3 new versions of the CHAQ were more sensitive at differentiating patients from controls (relative efficiency 1.35–1.65); the versions with 8 added items were even more sensitive (relative efficiency 1.79–2.32). The new versions of the CHAQ suffered less from a ceiling effect and were more normally distributed. Concordance between children and parents was moderate to high for all versions.ConclusionResearchers and clinicians should consider using a revision of the CHAQ. By being more sensitive at differentiating patients, the revised versions of the CHAQ will allow fewer subjects to be studied and will be more able to detect differences between patients in the clinic.
Feasibility and construct validity of the parent willingness‐to‐pay technique for children with juvenile idiopathic arthritis
Authors: Barron Andrea C. , Lee Tsz‐Leung , Taylor Janalee , Moore Terry , Passo Murray H. , Graham T. Brent , Griffin Thomas A. , Grom Alexei A. , Lovell Daniel J. , Brunner Hermine I. 
Published: December 2004

AbstractObjectiveTo assess the feasibility and construct validity of the willingness‐to‐pay (WTP) technique for measuring health care preferences in families of children with juvenile idiopathic arthritis (JIA).MethodsParents were asked to estimate the monthly US dollar amount they would be willing to pay to obtain for their child the following hypothetical drugs: ARTHRO, which guarantees complete clinical response; and NO‐STOM‐ACHE, a drug that eliminates gastrointestinal (GI) symptoms. A yes/no question was used with random assignment of the starting bids. Parents who agreed to pay the starting bid were then asked whether they would be willing to pay 200% and then 400% of this initial bid. Socioeconomic data and information on medications, disease activity, patient physical function, wellbeing, and health‐related quality of life (HRQOL) were obtained.ResultsSixty‐two families of children with JIA were interviewed. GI symptoms were present in 54%, and 53% of the children had joints with active arthritis or limited range of motion. Four parents (7%) were unwilling to pay anything for any of the studied medications. The mean amount (median; mean percentage of available family income) families were willing to pay was $395 ($300; 15%) for ARTHRO and $109 ($80; 4%) for NO‐STOM‐ACHE. Correlation and regression analysis supported that, adjusted for the available family income, the WTP for ARTHRO was associated with disease activity, pain, and the HRQOL of the patients. After correction for the starting bids and the available family income, the WTP for NO‐STOM‐ACHE was associated with the patient's HRQOL, pain, and the amount of GI discomfort.ConclusionThe WTP technique is feasible and has construct validity for measuring health care preferences for children with JIA. Relatively large WTP estimates support a possible important negative impact of the disease on families of children with JIA.
Risk of pancreatic adenocarcinoma
Authors: Chang Kenneth J. , Parasher Gulshan , Christie Catherine , Largent Joan , Anton‐Culver Hoda 
Published: December 2004

AbstractBACKGROUNDAfrican Americans have a higher incidence of pancreatic adenocarcinoma compared with non‐Hispanic whites. Whether other clinical differences exist between these two groups is not well known.METHODSThe authors conducted a population‐based retrospective analysis of all patients with pancreatic adenocarcinoma in both a regional and a statewide database between 1988 and 1998. Their goal was to evaluate differences in incidence rates, clinical presentation, including age at diagnosis, gender, and tumor characteristics, and treatment among race/ethnic groups.RESULTSAfrican Americans had a higher age‐adjusted incidence rate of pancreatic adenocarcinoma (8.78) compared with non‐Hispanic whites (5.89), Hispanics (5.09), Asians (4.75), and all race/ethnicities combined (5.82). African Americans also presented at a later stage of disease and received less surgery than all other race/ethnicities, despite equal availability of medical insurance. The analyses also revealed gender differences. In general, males maintained a higher incidence rate of pancreatic adenocarcinoma than females across all race/ethnicities. In all race/ethnic groups, females were diagnosed at an older age and an earlier stage of disease than males. The proportional hazard mortality ratio for females age < 60 was significantly less than that for males in the same age group (P < 0.02), even after accounting for stage and treatment.CONCLUSIONSAfrican Americans in California had a higher incidence rate of pancreatic adenocarcinoma, had a slightly higher risk of presenting with advanced‐stage diseas and with nonresectable tumors (i.e., tumors located in the body or tail of the pancreas), and underwent less surgical treatment than all other race/ethnicities. Younger females in all race/ethnic groups had a survival advantage over males of the same age. Cancer 2005. © 2004 American Cancer Society.
Lack of association of polyomavirus and herpesvirus types 6 and 7 in human lymphomas
Authors: Hernández‐Losa Javier , Fedele Cesar Giovanni , Pozo Francisco , Tenorio Antonio , Fernández Victor , Castellví Josep , Parada Carlos , Ramón y Cajal Santiago 
Published: December 2004

AbstractBACKGROUNDThe association of viruses with several human tumors has been studied for almost 100 years, and it remains a very controversial issue. Due to the fact that the presence of polyomaviruses and herpes viruses reportedly are associated with lymphomas, albeit with striking results and differences between the many studies, the authors undertook a study into the presence of viral sequences of polyomavirus (BK virus, JC virus, and especially simian virus 40 [SV40]) in human lymphomas in an attempt to explain this contradictory association. To complete the study, the presence of different virus types from the herpesviriridae family were analyzed, such as herpesvirus type 6 (HHV6), HHV7, HHV8, and Epstein–Barr virus, in human lymphomas.METHODSDNA was isolated from 83 frozen human lymphoma samples, and different polymerase chain reaction techniques were used to find polyomavirus and herpesvirus sequences in these samples. To assess the incidence of the presence of sequences in lymphomas, a parallel analysis was made of 53 samples from normal donor spleen lymphocytes. Positive samples were analyzed for polyomavirus sequences by immunohistochemistry.RESULTSPolyomavirus sequences were detected in 9 of 83 lymphomas (11%), and SV40 sequences could be confirmed in only 1 lymphoma. Immunohistochemistry for large‐T antigen was negative in all samples. Herpesviruses were detected in 53 of 83 lymphomas (63.9%), were detected more frequently in Hodgkin lymphomas (80%) than in non‐Hodgkin lymphomas (58.7%), and were detected in > 60% of normal spleen lymphocytes.CONCLUSIONSThe current results did not support a clear association of polyomavirus and HHV6 or HHV7 with lymphomas; HHV6 and HHV7 sequences were detected in a similar percentage of normal samples and lymphomas. The lack of significant differences between normal and malignant lymphocytes and the absence of viral protein expression in the tumor cells did not allow the establishment of a clinical correlation between polyomaviruses or HHVs (HHV6, HHV7, HHV8) and lymphomas. Nevertheless, because viral products can be lost during tumor progression, and because host factors can modulate the oncogenic role of some viruses, the hypothetical role of these viruses cannot be discarded completely. Cancer 2005. © 2004 American Cancer Society.
Prolegomenon to a history of paleoanthropology: The study of human origins as a scientific enterprise. Part 2. Eighteenth to the twentieth century
Authors: Goodrum Matthew R. 
Published: December 2004

AbstractModern scientific theories of human origins can be traced directly back to the discoveries, arguments, and theories of the seventeenth century. But as we have seen in the first part of this paper, a great many critical steps had been taken, ideas proposed, and discoveries made long before this. The scientific advances of the sixteenth and seventeenth centuries owed much to ancient science, while still retaining many aspects of the medieval Christian world view. Yet both science and Christianity changed significantly as a result of the Renaissance, the Protestant Reformation, the Scientific Revolution, the voyages of exploration, and the changes wrought on European society as a result of industrialization. The question of human origins was directly affected by the archeological study of prehistoric ruins, new geological theories, the study of fossils, the discovery of “savage” peoples living in the New World, and the comparison of prehistoric stone implements from Europe with those collected in the New World. This proliferation of new discoveries, new theories, and the emergence of completely new scientific disciplines in the seventeenth century laid the foundation for the dramatic new discoveries and theories that came over the next three centuries.
Holes in the head: Evolutionary interpretations of the paranasal sinuses in catarrhines
Authors: Rae Todd C. , Koppe Thomas 
Published: December 2004

AbstractEveryone who has ever experienced a head cold is familiar with the paranasal sinuses, the bony hollows above and beside the nasal cavity that contribute, sometimes painfully, to upper respiratory tract disorders. These internal cranial structures have a wide distribution among eutherian mammals and archosaurs.1, 2 Sinuses have languished somewhat in the shadow of their better known and more accessible morphological cousins (dentition, postcrania), but new imaging techniques, growth studies, and explicit phylogenetic evaluation3 are beginning to fill in the gaps in our knowledge of the evolution of these enigmatic spaces in primates and promise to yield insights into the evolution of the facial skeleton.