bluuebunny/crossref_metadata_2025_split huggingface dataset:
Antiprogesterone therapy uncouples axonal loss from demyelination in a transgenic rat model of CMT1A neuropathy
Authors: Meyer zu Horste Gerd , Prukop Thomas , Liebetanz David , Mobius Wiebke , Nave Klaus‐Armin , Sereda Michael W. 
Published: February 2007

AbstractObjectiveCharcot–Marie–Tooth disease (CMT) is the most common inherited neuropathy, and a duplication of the Pmp22 gene causes the most frequent subform CMT1A. Using a transgenic rat model of CMT1A, we tested the hypothesis that long‐term treatment with anti‐progesterone (Onapristone) reduces Pmp22 overexpression and improves CMT disease phenotype of older animals, thereby extending a previous proof‐of‐concept observation in a more clinically relevant setting.MethodsWe applied placebo‐controlled progesterone‐antagonist therapy to CMT rats for 5 months and performed grip‐strength analysis to assess the motor phenotype. Quantitative Pmp22 RT‐PCR and complete histological analysis of peripheral nerves and skin biopsies were performed.ResultsAnti‐progesterone therapy significantly increased muscle strength and muscle mass of CMT rats and reduced the performance difference to wildtype rats by about 50%. Physical improvements can be explained by the prevention of axon loss. Surprisingly, the effects of anti‐progesterone were not reflected by improved myelin sheath thickness. Electrophysiology confirmed unaltered NCV, but less reduced CMAP recordings in the treatment group. Moreover, the reduction of Pmp22 mRNA, as quantified in cutaneous nerves, correlated with the clinical phenotype at later stages.InterpretationProgesterone‐antagonist treatment. Pmp22 overexpression to a degree at which the axonal support function of Schwann cells is better maintained than myelination. This suggests that axonal loss in CMT1A is not caused by demyelination, but rather by a Schwann cell defect that has been partially uncoupled by anti‐progesterone treatment. Pmp22 expression analysis in skin may provide a prognostic marker for disease severity and for monitoring future clinical trials. Ann Neurol 2007;61:61–72
Paraneoplastic anti–N‐methyl‐D‐aspartate receptor encephalitis associated with ovarian teratoma
Authors: Dalmau Josep , Tüzün Erdem , Wu Hai‐yan , Masjuan Jaime , Rossi Jeffrey E. , Voloschin Alfredo , Baehring Joachim M. , Shimazaki Haruo , Koide Reiji , King Dale , Mason Warren , Sansing Lauren H. , Dichter Marc A. , Rosenfeld Myrna R. , Lynch David R. 
Published: February 2007

AbstractObjectiveTo report the autoantigens of a new category of treatment‐responsive paraneoplastic encephalitis.MethodsAnalysis of clinical features, neuropathological findings, tumors, and serum/cerebrospinal fluid antibodies using rat tissue, neuronal cultures, and HEK293 cells expressing subunits of the N‐methyl‐D‐aspartate receptor (NMDAR).ResultsTwelve women (14–44 years) developed prominent psychiatric symptoms, amnesia, seizures, frequent dyskinesias, autonomic dysfunction, and decreased level of consciousness often requiring ventilatory support. All had serum/cerebrospinal fluid antibodies that predominantly immunolabeled the neuropil of hippocampus/forebrain, in particular the cell surface of hippocampal neurons, and reacted with NR2B (and to a lesser extent NR2A) subunits of the NMDAR. NR2B binds glutamate and forms heteromers (NR1/NR2B or NR1/NR2A/NR2B) that are preferentially expressed in the adult hippocampus/forebrain. Expression of functional heteromers (not single subunits) was required for antibody binding. Eleven patients had teratoma of the ovary (six mature) and one a mature teratoma in the mediastinum; five of five tumors examined contained nervous tissue that strongly expressed NR2 subunits and reacted with patients' antibodies. Tumor resection and immunotherapy resulted in improvement or full recovery of eight of nine patients (paralleled by decreased antibody titers); two of three patients without tumor resection died of neurological deterioration. Autopsies showed extensive microgliosis, rare T‐cell infiltrates, and neuronal degeneration predominantly involving, but not restricted to, the hippocampus.InterpretationAntibodies to NR2B‐ and NR2A‐containing heteromers of the NMDAR associate with a severe but treatment‐responsive encephalitis. Our findings provide a diagnostic test and suggest a model of autoimmune NMDAR‐related encephalitis with broad implications for other immune‐mediated disorders of memory, behavior, and cognition. Ann Neurol 2007;61:25–36
Two novel benzenedicarboxylate‐metal complexes: synthesis, crystal structures and fluorescent properties
Authors: Song Yi‐Shan , Yan Bing , Chen Zhen‐Xia 
Published: February 2007

AbstractTwo novel benzenedicarboxylate–metal complexes, [Sm(nphth)(Hnphth)(H2O)3•H2O]2 and [Zn(nphth)(bipy)(H2O) •H2O]2 (2) (H2nphth = 3‐nitrophthalic acid, bipy = 2,2′‐bipyridine), have been synthesized under hydrothermal condition and characterized by single‐crystal X‐ray diffraction. Both complex 1 and 2 exhibit a dimeric structure, and nphth ligand shows different coordination mode in the f‐block and d‐block complexes. The fluorescent properties of two complexes are investigated; the results reveal that the two complexes show different kinds of fluorescence. Copyright © 2007 John Wiley & Sons, Ltd.
Longitudinal examination of lipid profiles in pediatric systemic lupus erythematosus
Authors: Sarkissian Talin , Beyene Joseph , Feldman Brian , McCrindle Brian , Silverman Earl D. 
Published: February 2007

AbstractObjectiveLipid abnormalities in patients with systemic lupus erythematosus (SLE) are common and are likely to be one of the causes of premature atherosclerosis in these patients. This study was undertaken to serially examine the lipid profile in pediatric patients with SLE to determine the roles of active disease and therapy in altering lipid levels.MethodsSerial lipid measurements were obtained in an inception cohort of 139 pediatric patients with SLE at the time of treatment with either a constant dose or differing doses of prednisone, and annually. The levels of cholesterol, triglycerides, low‐density lipoprotein (LDL), and high‐density lipoprotein (HDL) were correlated with measures of disease activity and prednisone dose.ResultsAt the time of SLE diagnosis in this pediatric cohort, the mean values for all lipids were abnormal. With each reduction in prednisone dose, there was a statistically significant decrease in cholesterol and triglyceride levels (P < 0.001) but not HDL or LDL levels. Nephrotic‐range proteinuria was associated with altered cholesterol, triglyceride, and LDL levels, whereas changes in HDL were more commonly associated with active nephritis. In the absence of nephrotic‐range proteinuria, increases in prednisone dose were associated with increased levels of all lipids, including HDL.ConclusionActive SLE leads to a proatherogenic lipid profile. Levels of cholesterol and LDL were mainly associated with the dose of prednisone, and were abnormal only during very high disease activity. Triglyceride levels were mainly associated with proteinuria, while changes in HDL were associated with active SLE and a high dose of prednisone. Our results suggest that the lipid profile in pediatric SLE is the result of a complex interaction of disease manifestations and the effects of prednisone therapy.
The HLA–DRB1 shared epitope alleles differ in the interaction with smoking and predisposition to antibodies to cyclic citrullinated peptide
Authors: van der Helm‐van Mil Annette H. M. , Verpoort Kirsten N. , le Cessie Saskia , Huizinga Tom W. J. , de Vries René R. P. , Toes René E. M. 
Published: February 2007

AbstractObjectiveThe HLA shared epitope (SE) alleles are primarily a risk factor for the presence of antibodies to cyclic citrullinated peptide (anti‐CCP antibodies) rather than for the development of rheumatoid arthritis (RA). The SE alleles interact with the environmental risk factor tobacco exposure (TE) for predisposition to anti‐CCP+ RA. The objectives of this study were to determine 1) whether different SE subtypes contribute differently to the presence of anti‐CCP antibodies, 2) whether different SE subtypes all interact with TE for the development of anti‐CCP antibodies, and 3) the effect of TE in relation to the SE alleles and anti‐CCP antibodies on the risk of progression from undifferentiated arthritis (UA) to RA.MethodsWe assessed the effect of SE subtypes and TE on the presence and level of anti‐CCP antibodies and on the risk of progression from UA to RA in 977 patients with early arthritis who were included in the Leiden Early Arthritis Clinic.ResultsThe HLA–DRB1*0401, *0404, *0405, or *0408 SE alleles conferred the highest risk of developing anti‐CCP antibodies (odds ratio [OR] 5.0, compared with an OR of 2.0 for the HLA–DRB1*0101 or *0102 SE alleles and an OR of 1.7 for the HLA–DRB1*1001 SE allele). Conversely, the TE–SE allele interaction was the strongest for the HLA–DRB1*0101 or *0102 SE alleles and the HLA–DRB1*1001 SE allele. TE in SE+, anti‐CCP+ patients correlated with higher levels of anti‐CCP antibodies and with progression from UA to RA. In logistic regression analysis, only the presence and level of anti‐CCP antibodies were associated independently with RA development.ConclusionThe HLA–DRB1 SE subtypes differ in their interaction with smoking and in their predisposition to anti‐CCP antibodies. TE contributes to the development of RA in SE+, anti‐CCP+ patients, which is explained by its effect on the level of anti‐CCP antibodies.
Systemic lupus erythematosus in a multiethnic US cohort: XLIII. The significance of thrombocytopenia as a prognostic factor
Authors: Fernández Mónica , Alarcón Graciela S. , Apte Mandar , Andrade Rosa M. , Vilá Luis M. , Reveille John D. 
Published: February 2007

AbstractObjectiveTo examine the clinical correlates of thrombocytopenia and the value of thrombocytopenia as a predictor of disease activity, damage accrual, and mortality in patients with systemic lupus erythematosus (SLE).MethodsSLE patients participating in a longitudinal multiethnic cohort were studied. Thrombocytopenia was defined as a platelet count <100,000/mm3 at or before enrollment (baseline). Patients were categorized by the presence and absence of thrombocytopenia. The impact of thrombocytopenia as well as severe thrombocytopenia (platelet count <50,000/mm3) on disease activity, damage accrual, and mortality was examined by multivariable analyses.ResultsA total of 616 patients were studied; 121 of the patients (20%) had thrombocytopenia, of whom 30 had severe thrombocytopenia. By univariable analyses, those with thrombocytopenia had more pulmonary, neurologic, renal, and hematologic involvement, worse disease activity and damage, and higher mortality rates. By multivariable analyses, thrombocytopenia was associated with higher disease activity over the disease course (P = 0.018), but not with the accrual of damage either at baseline (P = 0.543) or at the last visit (P = 0.086); however, severe thrombocytopenia was associated with damage accrual at the last visit (P = 0.020). When poverty was not included in the models, thrombocytopenia (<100,000/mm3 or <50,000/mm3) was strongly associated with mortality (P < 0.001 for each comparison); however, the level of significance decreased some when poverty was included in the models.ConclusionThrombocytopenia early in the course of SLE is indicative of more severe and active disease. Severe thrombocytopenia is an independent predictor of damage accrual at the last visit. Thrombocytopenia is also an independent predictor of mortality, albeit of a lesser magnitude than that predicted by poverty. Patients with thrombocytopenia need close monitoring for possible undesirable outcomes.
A prediction rule for disease outcome in patients with Recent‐onset undifferentiated arthritis: How to guide individual treatment decisions
Authors: van der Helm‐vanMil Annette H. M. , le Cessie Saskia , van Dongen Henrike , Breedveld Ferdinand C. , Toes René E. M. , Huizinga Tom W. J. 
Published: February 2007

AbstractObjectiveIn patients with undifferentiated arthritis (UA), methotrexate is effective for inhibiting symptoms, structural damage, and progression to rheumatoid arthritis (RA). However, 40–50% of patients with UA experience spontaneous remission. Thus, adequate decision‐making regarding treatment of patients with early UA requires identification of those patients in whom RA will develop.MethodsA prediction rule was developed using data from the Leiden Early Arthritis Clinic, an inception cohort of patients with recent‐onset arthritis (n = 1,700). The patients who presented with UA were selected (n = 570), and progression to RA or another diagnosis in this group was monitored for 1 year of followup. The clinical characteristics with independent predictive value for the development of RA were selected using logistic regression analysis. The diagnostic performance of the prediction rule was evaluated using the area under the curve (AUC). Cross‐validation controlled for overfitting of the data (internal validation). An independent cohort of patients with UA was used for external validation.ResultsThe prediction rule consisted of 9 clinical variables: sex, age, localization of symptoms, morning stiffness, the tender joint count, the swollen joint count, the C‐reactive protein level, rheumatoid factor positivity, and the presence of anti–cyclic citrullinated peptide antibodies. Each prediction score varied from 0 to 14 and corresponded to the percent chance of RA developing. For several cutoff values, the positive and negative predictive values were determined. The AUC values for the prediction rule, the prediction model after cross‐validation, and the external validation cohort were 0.89, 0.87, and 0.97, respectively.ConclusionIn patients who present with UA, the risk of developing RA can be predicted, thereby allowing individualized decisions regarding the initiation of treatment with disease‐modifying antirheumatic drugs in such patients.
Fcγ receptor type IIIA genotype and response to tumor necrosis factor α–blocking agents in patients with rheumatoid arthritis
Authors: Kastbom Alf , Bratt Johan , Ernestam Sofia , Lampa Jon , Padyukov Leonid , Söderkvist Peter , Skogh Thomas 
Published: February 2007

AbstractObjectiveTo determine whether a functional single‐nucleotide polymorphism in the gene encoding Fcγ receptor type IIIA (FcγRIIIA) correlates with the response to treatment with tumor necrosis factor α inhibitors in rheumatoid arthritis (RA).MethodsThe study population comprised 282 Swedish patients with RA in whom the therapeutic efficacy of conventional disease‐modifying antirheumatic drugs had been insufficient. Infliximab or etanercept treatment was initiated, and patients were evaluated after 3 months, using the American College of Rheumatology 20% improvement criteria (ACR20), the ACR50, and the ACR70 or the European League Against Rheumatism (EULAR) criteria. The chi‐square test was used to compare response rates across FcγRIIIA genotypes.ResultsNo differences in genotype distribution were observed among nonresponders compared with ACR20 responders (P = 0.80), ACR50 responders (P = 0.56), or ACR70 responders (P = 0.91). Similar results were observed when analyzing infliximab and etanercept separately or when using the EULAR response criteria.ConclusionUnlike the findings of a previous study, the results of the current study suggest that the 158V/F polymorphism of FcγRIIIA is very unlikely to influence the clinical efficacy of infliximab or etanercept in patients with RA.
Amelioration of collagen‐induced arthritis in rats by nanogold
Authors: Tsai Chiau‐Yuang , Shiau Ai‐Li , Chen Shih‐Yao , Chen Yu‐Hung , Cheng Pai‐Chiao , Chang Meng‐Ya , Chen Dong‐Hwang , Chou Chen‐Hsi , Wang Chrong‐Reen , Wu Chao‐Liang 
Published: February 2007

AbstractObjectiveAngiogenesis plays a part in the pathogenesis of rheumatoid arthritis (RA), and nanogold inhibits the activity of an angiogenic factor, vascular endothelial growth factor (VEGF). We therefore investigated whether intraarticular delivery of nanogold ameliorates collagen‐induced arthritis (CIA) in rats.MethodsBinding of 13‐nm nanogold to VEGF in human RA synovial fluid (SF) and its effects on RA SF–induced endothelial cell proliferation and migration were assessed. Nanogold was administered intraarticularly to rats with CIA before the onset of arthritis. Progression of CIA was monitored by measures of clinical, radiologic, and histologic changes. In addition, the microvessel density and extent of infiltrating macrophages as well as levels of tumor necrosis factor α (TNFα) and interleukin‐1β (IL‐1β) in the ankle joints were determined.ResultsNanogold bound to VEGF in RA SF, resulting in inhibition of RA SF–induced endothelial cell proliferation and migration. Significant reductions in ankle circumference, articular index scores, and radiographic scores were observed in the nanogold‐treated rats with CIA compared with their control counterparts. In addition, the histologic score (of synovial hyperplasia, cartilage erosion, and leukocyte infiltration), microvessel density, macrophage infiltration, and levels of TNFα and IL‐1β were also significantly reduced in the ankle joints of nanogold‐treated rats.ConclusionOur results are the first to demonstrate that intraarticular administration of nanogold ameliorates the clinical course of CIA in rats. Nanogold exerted antiangiogenic activities and subsequently reduced macrophage infiltration and inflammation, which resulted in attenuation of arthritis. These results demonstrate proof of principle for the use of nanogold as a novel therapeutic agent for the treatment of RA.
Identification of markers to characterize and sort human articular chondrocytes with enhanced in vitro chondrogenic capacity
Authors: Grogan Shawn Patrick , Barbero Andrea , Diaz‐Romero Jose , Cleton‐Jansen Anne‐Marie , Soeder Stephan , Whiteside Robert , Hogendoorn Pancras C. W. , Farhadi Jian , Aigner Thomas , Martin Ivan , Mainil‐Varlet Pierre 
Published: February 2007

AbstractObjectiveTo identify markers associated with the chondrogenic capacity of expanded human articular chondrocytes and to use these markers for sorting of more highly chondrogenic subpopulations.MethodsThe chondrogenic capacity of chondrocyte populations derived from different donors (n = 21) or different clonal strains from the same cartilage biopsy specimen (n = 21) was defined based on the glycosaminoglycan (GAG) content of tissues generated using a pellet culture model. Selected cell populations were analyzed by microarray and flow cytometry. In some experiments, cells were sorted using antibodies against molecules found to be associated with differential chondrogenic capacity and again assessed in pellet cultures.ResultsSignificance Analysis of Microarrays indicated that chondrocytes with low chondrogenic capacity expressed higher levels of insulin‐like growth factor 1 and of catabolic genes (e.g., matrix metalloproteinase 2, aggrecanase 2), while chondrocytes with high chondrogenic capacity expressed higher levels of genes involved in cell–cell or cell–matrix interactions (e.g., CD49c, CD49f). Flow cytometry analysis showed that CD44, CD151, and CD49c were expressed at significantly higher levels in chondrocytes with higher chondrogenic capacity. Flow cytometry analysis of clonal chondrocyte strains indicated that CD44 and CD151 could also identify more chondrogenic clones. Chondrocytes sorted for brighter CD49c or CD44 signal expression produced tissues with higher levels of GAG per DNA (up to 1.4‐fold) and type II collagen messenger RNA (up to 3.4‐fold) than did unsorted cells.ConclusionWe identified markers that allow characterization of the capacity of monolayer‐expanded chondrocytes to form in vitro cartilaginous tissue and enable enrichment for subpopulations with higher chondrogenic capacity. These markers might be used as a means to predict and possibly improve the outcome of cell‐based cartilage repair techniques.
Stimulation of DNA repair and increased light output in response to UV irradiation in Escherichia coli expressing lux genes
Authors: Cutter Kerry L. , Alloush Habib M. , Salisbury Vyv C. 
Published: February 2007

AbstractIt has previously been suggested that the evolutionary drive of bacterial bioluminescence is a mechanism of DNA repair. By assessing the UV sensitivity of Escherichia coli, it is shown that the survival of UV‐irradiated E. coli constitutively expressing luxABCDE in the dark is significantly better than either a strain with no lux gene expression or the same strain expressing only luciferase (luxAB) genes. This shows that UV resistance is dependent on light output, and not merely on luciferase production. Also, bacterial survival was found to be dependent on the conditions following UV irradiation, as bioluminescence‐mediated repair was not as efficient as repair in visible light. Moreover, photon emission revealed a dose‐dependent increase in light output per cell after UV exposure, suggesting that increased lux gene expression correlates with UV‐induced DNA damage. This phenomenon has been previously documented in organisms where the lux genes are under their natural luxR regulation but has not previously been demonstrated under the regulation of a constitutive promoter. Copyright © 2007 John Wiley & Sons, Ltd.
Influence of sex on expansion rate of abdominal aortic aneurysms
Authors: Mofidi R , Goldie V J , Kelman J , Dawson A R W , Murie J A , Chalmers R T A 
Published: February 2007

Abstract

Background
The UK Small Aneurysm Trial suggested that female sex is an independent risk factor for rupture of abdominal aortic aneurysm (AAA). This study assessed the effect of sex on the growth rate of AAA.

Methods
Between January 1985 and August 2005 all patients who were referred to the Royal Infirmary of Edinburgh with an AAA who were not considered for early aneurysm repair were assessed by serial abdominal ultrasonography. Maximum anteroposterior and transverse diameters of the AAAs were measured.

Results
A total of 1255 patients (824 men and 431 women) were followed up for a median of 30 (range 6–185) months. A median of six examinations (range 2–37) was performed for each patient. Median diameter on initial examination was 41 (range 25–83) mm. Median growth rate overall was 2·79 (range − 4·80–37·02) mm per year. Median growth rate of AAA was significantly greater in women than men (3·67 (range − 1·2–37·02) versus 2·03 (range − 4·80–21·00) mm per year; P &lt; 0·01). Weighted linear regression analysis revealed that large initial anteroposterior AAA diameter and female sex were significant predictors of faster aneurysm growth rate (P &lt; 0·001 and P = 0·006 respectively).

Conclusion
The growth rate of AAA was significantly greater in women than in men. This may have implications for the frequency of follow-up and timing of repair of AAA in women.