bluuebunny/crossref_metadata_2025 huggingface dataset:
HLA–DPB1 and DPB2 are genetic loci for systemic sclerosis: A genome‐wide association study in Koreans with replication in North Americans
Authors: Zhou Xiaodong , Lee Jong Eun , Arnett Frank C. , Xiong Momiao , Park Min Young , Yoo Yeon Kyeong , Shin Eun Soon , Reveille John D. , Mayes Maureen D. , Kim Jin Hyun , Song Ran , Choi Ji Yong , Park Ji Ah , Lee Yun Jong , Lee Eun Young , Song Yeong Wook , Lee Eun Bong
Published: November 2009

Objective

To identify systemic sclerosis (SSc) susceptibility loci via a genome‐wide association study.

Methods

A genome‐wide association study was performed in 137 patients with SSc and 564 controls from Korea using the Affymetrix Human SNP Array 5.0. After fine‐mapping studies, the results were replicated in 1,107 SSc patients and 2,747 controls from a US Caucasian population.

Results

The single‐nucleotide polymorphisms (SNPs) (rs3128930, rs7763822, rs7764491, rs3117230, and rs3128965) of HLA–DPB1 and DPB2 on chromosome 6 formed a distinctive peak with log P values for association with SSc susceptibility (P = 8.16 × 10−13). Subtyping analysis of HLA–DPB1 showed that DPB1*1301 (P = 7.61 × 10−8) and DPB1*0901 (P = 2.55 × 10−5) were the subtypes most susceptible to SSc in Korean subjects. In US Caucasians, 2 pairs of SNPs, rs7763822/rs7764491 and rs3117230/rs3128965, showed strong association with SSc patients who had either circulating anti–DNA topoisomerase I (P = 7.58 × 10−17/4.84 × 10−16) or anticentromere autoantibodies (P = 1.12 × 10−3/3.2 × 10−5), respectively.

Conclusion

The results of our genome‐wide association study in Korean subjects indicate that the region of HLA–DPB1 and DPB2 contains the loci most susceptible to SSc in a Korean population. The confirmatory studies in US Caucasians indicate that specific SNPs of HLA–DPB1 and/or DPB2 are strongly associated with US Caucasian patients with SSc who are positive for anti–DNA topoisomerase I or anticentromere autoantibodies.
Rapamycin versus methotrexate in early diffuse systemic sclerosis: Results from a randomized, single‐blind pilot study
Authors: Su Tien‐I Karleen , Khanna Dinesh , Furst Daniel E. , Danovitch Gabriel , Burger Christina , Maranian Paul , Clements Philip J.
Published: November 2009

Objective

To assess the safety and efficacy of rapamycin in the treatment of diffuse systemic sclerosis (SSc; scleroderma).

Methods

Eighteen patients with diffuse SSc of ≤5 years duration were randomized to receive rapamycin or methotrexate (MTX) in a single‐blind, 48‐week study. Abnormalities in clinical and laboratory parameters were compared between the 2 treatment groups. The potential efficacy of the study drugs was evaluated by comparing results of the baseline and 48‐week assessments, including the modified Rodnan skin thickness score (MRSS) and the Health Assessment Questionnaire disability index.

Results

The baseline characteristics of the patients were similar in both groups (n = 9 in each). One patient in the rapamycin group who never received the study drug was excluded from the analysis. Three patients in each group withdrew from the study; 2 of the withdrawals were treatment‐related (severe hypertriglyceridemia associated with rapamycin, and pancytopenia associated with MTX), and 4 were SSc‐related. Hypertriglyceridemia was the most notable side effect associated with rapamycin, but it was generally well tolerated and treatable. The incidence and severity of other adverse drug reactions were comparable between the 2 groups. Within each group, the MRSS improved significantly from baseline. In the rapamycin group, the patient's global assessment showed a significant improvement from baseline, while forced vital capacity values declined from baseline. The disease activity scores at 48 weeks and the changes in these scores from baseline were not significantly different between the 2 groups.

Conclusion

Rapamycin has a reasonable safety profile in a select group of patients with scleroderma. Larger trials are needed to assess the efficacy of rapamycin in patients with early diffuse SSc.
Depletion of functionally active CD20+ T cells by rituximab treatment
Authors: Wilk Esther , Witte Torsten , Marquardt Nicole , Horvath Tibor , Kalippke Katy , Scholz Kirsten , Wilke Nadine , Schmidt Reinhold E. , Jacobs Roland
Published: November 2009

Objective

Rituximab is a therapeutic anti‐CD20 antibody used for in vivo depletion of B cells in proliferative and autoimmune diseases. However, the mechanisms of action are not fully understood, since not all of the therapy‐mediated effects can be explained by the depletion of antibody‐secreting cells. In addition to B cells, there is also a small population of T cells coexpressing CD20 in all individuals. This study was conducted to examine the phenotype and function of CD3+CD20+ T cells in patients with rheumatoid arthritis (RA) and healthy controls.

Methods

The phenotype and apoptosis of peripheral blood mononuclear cells from healthy donors and RA patients were examined by 4‐color fluorescence‐activated cell sorting analyses. Cytokine production was determined by intracellular staining and measurement of cytokines in the supernatants. Proliferation of sorted T cell populations was analyzed using 3H‐thymidine uptake assays.

Results

In healthy individuals, 0.1–6.8% of peripheral blood T cells (mean 1.6%; n = 142) coexpressed CD20, which was not significantly different from that in the peripheral blood of RA patients, in whom 0.4–2.6% of T cells (mean 1.2%; n = 27) were CD20+. During rituximab therapy, the CD20+ T cells along with the B cells were eliminated from the RA peripheral blood. Among the CD20+ T cells, 45% coexpressed CD8 and 55% coexpressed CD4. Polyclonal CD3+CD20+ cells were functionally characterized by constitutive cytokine production (i.e., interleukin‐1β and tumor necrosis factor α), a low proliferative capacity, a high activation state, and enhanced susceptibility to apoptosis.

Conclusion

These findings suggest that CD20+ T cells represent a terminally differentiated cell type with immune‐regulatory and proinflammatory capacities. Depletion of CD20+ T cells may be an additional mechanism by which anti‐CD20 therapy functions in patients with RA.
A critical role of Cyr61 in interleukin‐17–dependent proliferation of fibroblast‐like synoviocytes in rheumatoid arthritis
Authors: Zhang Qiuyu , Wu Juanjuan , Cao Qi , Xiao Lianbo , Wang Li , He Dongyi , Ouyang Guilin , Lin Jinpiao , Shen Baihua , Shi Yuan , Zhang Yan , Li Dangsheng , Li Ningli
Published: November 2009

Objective

Fibroblast‐like synoviocytes (FLS) are a major component of the hyperplastic synovial pannus that aggressively invades cartilage and bone during the course of rheumatoid arthritis (RA). Cyr61 (CCN1) is a product of a growth factor–inducible immediate early gene and is involved in cell adhesion, proliferation, and differentiation. However, the role that Cyr61 plays in FLS proliferation has remained undetermined. The aim of this study was to identify the role of Cyr61 in regulating the proliferation of FLS derived from patients with RA.

Methods

Expression of Cyr61 in synovial tissue (ST) and in FLS was determined simultaneously using immunohistochemistry, real‐time polymerase chain reaction, and Western blotting. Cyr61 levels in synovial fluid (SF) were determined by enzyme‐linked immunosorbent assay. FLS proliferation stimulated by SF, Cyr61, and interleukin‐17 (IL‐17) was measured by thymidine incorporation. Activation of signal transduction pathways was determined by Western blotting and confocal microscopy.

Results

Cyr61 was overexpressed in ST, FLS, and SF samples from RA patients as compared with samples from normal controls. Elevated levels of Cyr61 in RA SF promoted the proliferation of FLS, an effect that was abrogated by a neutralizing monoclonal antibody against human Cyr61. Furthermore, in samples from RA patients, Cyr61 was found to protect FLS from apoptosis and to sustain the expression of Bcl‐2 in FLS. Most importantly, the expression of Cyr61 in FLS was regulated by IL‐17 mainly via the p38 MAPK and NF‐κB signaling pathways. Knockdown of expression of the Cyr61 gene inhibited IL‐17–stimulated FLS proliferation.

Conclusion

Our findings indicate that Cyr61 plays a critical role in IL‐17–mediated proliferation of FLS in RA and likely contributes to hyperplasia of synovial lining cells and eventually to joint destruction in patients with RA.
Rituximab may form a complex with iGmκ mixed cryoglobulin and induce severe systemic reactions in patients with hepatitis C virus–induced vasculitis
Authors: Sène Damien , Ghillani‐Dalbin Pascale , Amoura Zahir , Musset Lucile , Cacoub Patrice
Published: November 2009

Objective

To report on 6 cases of hepatitis C virus (HCV)–induced mixed cryoglobulinemia (MC) vasculitis in patients who developed severe systemic reactions after rituximab infusion, and to report the results of the in vitro analysis of the underlying immunologic mechanisms.

Methods

Twenty‐two HCV‐infected patients with MC vasculitis received rituximab infusions (a low‐dose protocol cycle with 375 mg/m2/week for 4 consecutive weeks in 18 patients and a high‐dose protocol cycle with 1,000 mg on days 1 and 15 in 4 patients). Systemic drug reactions following rituximab infusion were recorded and analyzed clinically and immunochemically.

Results

Six of 22 patients (27.3%) experienced systemic drug reactions after rituximab infusion. Four patients developed a severe flare of MC vasculitis 1 or 2 days after rituximab infusion. Two patients developed serum sickness syndrome 7 and 9 days after the first 1,000 mg rituximab infusion. Compared with patients without drug reactions, those with drug reactions had higher mixed cryoglobulin levels (mean ± SD 1.4 ± 0.82 gm/liter versus 0.71 ± 0.77 gm/liter; P = 0.0475) and lower C4 levels (mean ± SD 0.02 ± 0.006 gm/liter versus 0.07 ± 0.07 gm/liter; P = 0.02), and more of them received 1,000 mg high‐dose rituximab protocol (50% versus 6.25%; P = 0.046). In vitro immunochemical assays showed that rituximab formed a complex with the cryoprecipitating IgMκ that had rheumatoid factor (RF) activity. Moreover, the in vitro addition of rituximab to serum containing an RF‐positive IgMκ type II mixed cryoglobulin was associated with visibly accelerated cryoprecipitation.

Conclusion

In HCV‐associated MC vasculitis, rituximab may form a complex with RF‐positive IgMκ, leading to accelerated cryoprecipitation and to severe systemic reactions. Rituximab should be administered with caution in MC vasculitis, with use of the 375 mg protocol and plasma exchanges prior to rituximab infusion in patients with high baseline levels of mixed cryoglobulin.
Matrix metalloproteinase 13–deficient mice are resistant to osteoarthritic cartilage erosion but not chondrocyte hypertrophy or osteophyte development
Authors: Little C. B. , Barai A. , Burkhardt D. , Smith S. M. , Fosang A. J. , Werb Z. , Shah M. , Thompson E. W.
Published: November 2009

Objective

To investigate the role of matrix metalloproteinase 13 (MMP‐13; collagenase 3) in osteoarthritis (OA).

Methods

OA was surgically induced in the knees of MMP‐13–knockout mice and wild‐type mice, and mice were compared. Histologic scoring of femoral and tibial cartilage aggrecan loss (0–3 scale), erosion (0–7 scale), and chondrocyte hypertrophy (0–1 scale), as well as osteophyte size (0–3 scale) and maturity (0–3 scale) was performed. Serial sections were stained for type X collagen and the MMP‐generated aggrecan neoepitope DIPEN.

Results

Following surgery, aggrecan loss and cartilage erosion were more severe in the tibia than femur (P < 0.01) and tibial cartilage erosion increased with time (P < 0.05) in wild‐type mice. Cartilaginous osteophytes were present at 4 weeks and underwent ossification, with size and maturity increasing by 8 weeks (P < 0.01). There was no difference between genotypes in aggrecan loss or cartilage erosion at 4 weeks. There was less tibial cartilage erosion in knockout mice than in wild‐type mice at 8 weeks (P < 0.02). Cartilaginous osteophytes were larger in knockout mice at 4 weeks (P < 0.01), but by 8 weeks osteophyte maturity and size were no different from those in wild‐type mice. Articular chondrocyte hypertrophy with positive type X collagen and DIPEN staining occurred in both wild‐type and knockout mouse joints.

Conclusion

Our findings indicate that structural cartilage damage in a mouse model of OA is dependent on MMP‐13 activity. Chondrocyte hypertrophy is not regulated by MMP‐13 activity in this model and does not in itself lead to cartilage erosion. MMP‐13 deficiency can inhibit cartilage erosion in the presence of aggrecan depletion, supporting the potential for therapeutic intervention in established OA with MMP‐13 inhibitors.
Joint replacement surgeries among medicare beneficiaries in rural compared with urban areas
Authors: Francis Mark L. , Scaife Steven L. , Zahnd Whitney E. , Cook E. Francis , Schneeweiss Sebastian
Published: November 2009

Objective

People in rural areas live farther away from hospitals than do people in urban areas. Thus, there is concern that people living in rural areas may be less willing or able to undergo elective surgical procedures. This study was undertaken to determine whether Medicare beneficiaries in rural areas were less likely to have elective total knee or hip replacement surgeries compared with their urban counterparts.

Methods

We performed a cross‐sectional study of Medicare beneficiaries, controlling for age, sex, race/ethnicity, and economic status. Beneficiaries were assigned to rural versus urban areas based on their zip code of residence and the 10‐point Rural‐Urban Commuting Area designation. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated.

Results

Compared with urban beneficiaries, rural beneficiaries were 27% more likely to have total knee or hip replacement surgeries (OR 1.27 [95% CI 1.26–1.28]). After adjusting for age, sex, race/ethnicity, median household income, average house value, mean poverty ratio, and state of residence, rural beneficiaries were still 14% more likely to have total joint replacement surgeries (OR 1.14 [95% CI 1.13–1.16]). Differential use of surgery before and after receiving Medicare eligibility did not explain the findings. While significant sex, racial, and ethnic disparities were present in both rural and urban areas, for the most part these disparities were ameliorated rather than accentuated in rural areas.

Conclusion

Contrary to expectations, our findings indicate that Medicare beneficiaries living in rural areas are more likely to undergo total knee or hip replacement surgeries.
Inflammatory arthritis in caspase 1 gene–deficient mice: Contribution of proteinase 3 to caspase 1–independent production of bioactive interleukin‐1β
Authors: Joosten Leo A. B. , Netea Mihai G. , Fantuzzi Giamila , Koenders Marije I. , Helsen Monique M. A. , Sparrer Helmut , Pham Christine T. , van der Meer Jos W. M. , Dinarello Charles A. , van den Berg Wim B.
Published: November 2009

Objective

Caspase 1, a known cysteine protease, is a critical component of the inflammasome. Both caspase 1 and neutrophil serine proteases such as proteinase 3 (PR3) can process pro–interleukin‐1β (proIL‐1β), a crucial cytokine linked to the pathogenesis of rheumatoid arthritis. This study was undertaken to establish the relative importance of caspase 1 and serine proteases in mouse models of acute and chronic inflammatory arthritis.

Methods

Acute and chronic arthritis were induced in caspase 1−/− mice, and the lack of caspase 1 was investigated for its effects on joint swelling, cartilage metabolism, and histopathologic features. In addition, caspase 1 activity was inhibited in mice lacking active cysteine proteases, and the effects of dual blockade of caspase 1 and serine proteases on arthritis severity and histopathologic features were evaluated.

Results

Surprisingly, caspase 1−/− mice, in a model of acute (neutrophil‐dominated) arthritis, developed joint swelling to an extent similar to that in wild‐type control mice. Joint fluid concentrations of bioactive IL‐1β were comparable in caspase 1−/− mice and controls. In contrast, induction of chronic arthritis (characterized by minimal numbers of neutrophils) in caspase 1−/− mice led to reduced joint inflammation and less cartilage damage, implying a caspase 1–dependent role in this process. In mice lacking neutrophil serine PR3, inhibition of caspase 1 activity resulted in decreased bioactive IL‐1β concentrations in the synovial tissue and less suppression of chondrocyte anabolic function. In addition, dual blockade of both PR3 and caspase 1 led to protection against cartilage and bone destruction.

Conclusion

Caspase 1 deficiency does not affect neutrophil‐dominated joint inflammation, whereas in chronic arthritis, the lack of caspase 1 results in reduced joint inflammation and cartilage destruction. These findings suggest that inhibitors of caspase 1 are not able to interfere with the whole spectrum of IL‐1β production, and therefore such inhibitors may be of therapeutic value only in inflammatory conditions in which limited numbers of neutrophils are present.
Do mothers and fathers hold similar views about their child's arthritis?
Authors: Mulligan Kathleen , Etheridge Angela , Kassoumeri Laura , Wedderburn Lucy R. , Newman Stanton
Published: November 2009

Objective

Evaluations of the well‐being of children with juvenile idiopathic arthritis (JIA) typically rely on parents as proxy respondents. An assumption of several studies appears to be that mothers' and fathers' ratings are interchangeable, as reports do not always specify which parent completed the assessments nor, in repeated measures, whether they were completed by the same parent. The aim of this study was to examine the level of agreement between mothers' and fathers' ratings of their child's quality of life (QOL) and to identify possible predictors of disagreement.

Methods

Mothers and fathers (n = 82) of children with JIA completed ratings of their child's symptoms, QOL, and measures of their mood and beliefs about their child's illness and treatment. The number of active and limited joints and the physician's global assessment were also recorded.

Results

Intraclass correlation coefficients between mothers' and fathers' ratings of physical and psychosocial QOL were high (0.824 and 0.755, respectively). However, calculation of difference scores revealed that 70.6% and 65.9%, respectively, were classified as discordant. Where parents differed, the direction of difference was not systematic. Discordance in parents' mood states and in their illness and treatment beliefs explained a small amount of the variance in discordance in QOL.

Conclusion

It should not be assumed that proxy ratings of a child's well‐being can be generalized from one parent to the other. Studies that take repeated assessments should ensure that the same parent completes assessments at all time points. Other factors that may explain discordance between parents' ratings need to be explored.
Neurologic outcome of surgical and conservative treatment of rheumatoid cervical spine subluxation: A systematic review
Authors: Wolfs Jasper F. C. , Kloppenburg Margreet , Fehlings Michael G. , van Tulder Maurits W. , Boers Maarten , Peul Wilco C.
Published: November 2009

Objective

Rheumatoid arthritis commonly involves the upper cervical spine and can cause significant neurologic morbidity and mortality. However, there is no consensus on the optimal timing for surgical intervention: whether surgery should be performed prophylactically or once neurologic deficits have become apparent.

Methods

A systematic review of the literature was performed to analyze neurologic outcome (Ranawat) and survival time (Kaplan‐Meier) after surgical or conservative treatment using the MOOSE (Meta‐analysis Of Observational Studies in Epidemiology) and GRADE (Grading of Recommendations, Assessment, Development and Evaluation system) criteria.

Results

Twenty‐five observational studies were selected. No randomized controlled trials (RCTs) could be found. All of the studies had a high risk of bias. Twenty‐three studies reported the neurologic outcome after surgery for 752 patients. Neurologic deterioration rarely occurred in Ranawat I and II patients. Ranawat III patients did not fully recover. The 10‐year survival rates were 77%, 63%, 47%, and 30% for Ranawat I, II, IIIA, and IIIB, respectively. The Ranawat IIIB patients had a significantly worse outcome. Another 185 patients treated conservatively were described in 7 studies. Neurologic deterioration rarely occurred in Ranawat I patients, but was almost inevitable in Ranawat II, IIIA, and IIIB patients. The Kaplan‐Meier analysis showed a 10‐year overall survival rate of 40%.

Conclusion

There are no RCTs that compared surgery with conservative treatment. In observational studies, surgical neurologic outcomes were better than conservative treatment in all patients with cervical spine involvement, and in asymptomatic patients with no neurologic impairment (Ranawat I) the outcomes were similar; however, the evidence is weak. Survival time of surgical and conservative treatment could not be compared.
Trabecular morphometry by fractal signature analysis is a novel marker of osteoarthritis progression
Authors: Kraus Virginia Byers , Feng Sheng , Wang ShengChu , White Scott , Ainslie Maureen , Brett Alan , Holmes Anthony , Charles H. Cecil
Published: November 2009

Objective

To evaluate the effectiveness of using subchondral bone texture observed on a radiograph taken at baseline to predict progression of knee osteoarthritis (OA) over a 3‐year period.

Methods

A total of 138 participants in the Prediction of Osteoarthritis Progression study were evaluated at baseline and after 3 years. Fractal signature analysis (FSA) of the medial subchondral tibial plateau was performed on fixed flexion radiographs of 248 nonreplaced knees, using a commercially available software tool. OA progression was defined as a change in joint space narrowing (JSN) or osteophyte formation of 1 grade according to a standardized knee atlas. Statistical analysis of fractal signatures was performed using a new model based on correlating the overall shape of a fractal dimension curve with radius.

Results

Fractal signature of the medial tibial plateau at baseline was predictive of medial knee JSN progression (area under the curve [AUC] 0.75, of a receiver operating characteristic curve) but was not predictive of osteophyte formation or progression of JSN in the lateral compartment. Traditional covariates (age, sex, body mass index, knee pain), general bone mineral content, and joint space width at baseline were no more effective than random variables for predicting OA progression (AUC 0.52–0.58). The predictive model with maximum effectiveness combined fractal signature at baseline, knee alignment, traditional covariates, and bone mineral content (AUC 0.79).

Conclusion

We identified a prognostic marker of OA that is readily extracted from a plain radiograph using FSA. Although the method needs to be validated in a second cohort, our results indicate that the global shape approach to analyzing these data is a potentially efficient means of identifying individuals at risk of knee OA progression.
Amelioration of brain pathology and behavioral dysfunction in mice with lupus following treatment with a tolerogenic peptide
Authors: Lapter Smadar , Marom Anat , Meshorer Asher , Elmann Anat , Sharabi Amir , Vadai Ezra , Neufeld Adi , Sztainberg Yejezkel , Gil Shoshana , Getselter Dmitriy , Chen Alon , Mozes Edna
Published: November 2009

Objective

Central nervous system (CNS) involvement in systemic lupus erythematosus (SLE) is manifested by neurologic deficits and psychiatric disorders. The aim of this study was to examine SLE‐associated CNS pathology in lupus‐prone (NZB × NZW)F1 (NZB/NZW) mice, and to evaluate the ameliorating effects of treatment with a tolerogenic peptide, hCDR1 (human first complementarity‐determining region), on these manifestations.

Methods

Histopathologic analyses of brains from lupus‐prone NZB/NZW mice treated with vehicle, hCDR1, or a control scrambled peptide were performed. The messenger RNA expression of SLE‐associated cytokines and apoptosis‐related molecules from the hippocampi was determined. Anxiety‐like behavior was assessed by open‐field tests and dark/light transfer tests, and memory deficit was assessed using a novel object recognition test.

Results

Infiltration was evident in the hippocampi of the lupus‐afflicted mice, and the presence of CD3+ T cells as well as IgG and complement C3 complex deposition was observed. Furthermore, elevated levels of gliosis and loss of neuronal nuclei immunoreactivity were also observed in the hippocampi of the mice with lupus. Treatment with hCDR1 ameliorated the histopathologic changes. Treatment with hCDR1 down‐regulated the high expression of interleukin‐1β (IL‐1β), IL‐6, IL‐10, interferon‐γ, transforming growth factor β, and the proapoptotic molecule caspase 8 in the hippocampi of the mice with lupus, and up‐regulated expression of the antiapoptotic bcl‐xL gene. Diseased mice exhibited increased anxiety‐like behavior and memory deficit. Treatment with hCDR1 improved these parameters, as assessed by behavior tests.

Conclusion

Treatment with hCDR1 ameliorated CNS pathology and improved the tested cognitive and mood‐related behavior of the mice with lupus. Thus, hCDR1 is a novel candidate for the treatment of CNS lupus.
Denuded subchondral bone and knee pain in persons with knee osteoarthritis
Authors: Moisio Kirsten , Eckstein Felix , Chmiel Joan S. , Guermazi Ali , Prasad Pottumarthi , Almagor Orit , Song Jing , Dunlop Dorothy , Hudelmaier Martin , Kothari Ami , Sharma Leena
Published: November 2009

Objective

It is unclear how articular cartilage loss contributes to pain in patients with knee osteoarthritis (OA). Full‐thickness cartilage defects expose the subchondral bone plate. The relationship between denuded bone and pain has not been examined. The aim of this study was to investigate whether the percent of denuded bone is associated with moderate‐to‐severe knee pain or frequent knee pain and longitudinally with frequent knee pain 2 years after the baseline evaluation.

Methods

We studied 182 persons with knee OA (305 knees). Applying specialized magnetic resonance imaging techniques, manual segmentation was used to compute cartilage‐covered and denuded bone areas for each surface. Moderate‐to‐severe knee pain was defined as a score of ≥40 mm on a knee‐specific 100‐mm visual analog scale, and frequent knee pain was defined as pain on most days during the past month. Logistic regression and generalized estimating equations were used in analyses, adjusting for age, sex, body mass index, and bone marrow lesions.

Results

Cross‐sectional analyses revealed that moderate‐to‐severe knee pain was associated with percent denuded bone in the medial compartment (adjusted odds ratio [OR] 3.90, 95% confidence interval [95% CI] 1.33–11.47), in the medial and patellar surfaces together, and in the lateral and patellar surfaces. Frequent knee pain was associated with percent denuded bone in the patellar surface (adjusted OR 3.11, 95% CI 1.24–7.81), in the medial and patellar surfaces, and in the lateral and patellar surfaces. Longitudinal analyses (in 168 knees without frequent knee pain at baseline) revealed that percent denuded bone in the medial and patellar surfaces was associated with frequent incident knee pain (adjusted OR 4.19, 95% CI 1.56–11.22).

Conclusion

These results support a relationship between subchondral bone plate exposure and prevalent and incident knee pain in patients with knee OA.
A novel subpopulation of B‐1 cells is enriched with autoreactivity in normal and lupus‐prone mice
Authors: Zhong Xuemei , Lau Stanley , Bai Chunyan , Degauque Nicolas , Holodick Nichol E. , Steven Scott J. , Tumang Joseph , Gao Wenda , Rothstein Thomas L.
Published: November 2009

Objective

B‐1 cells have long been suggested to play an important role in lupus. However, reports to date have been controversial regarding their pathogenic or protective roles in different animal models. We undertook this study to investigate a novel subpopulation of B‐1 cells and its roles in murine lupus.

Methods

Lymphocyte phenotypes were assessed by flow cytometry. Autoantibody secretion was analyzed by enzyme‐linked immunosorbent assay, autoantigen proteome array, and antinuclear antibody assay. Cell proliferation was measured by thymidine incorporation and 5,6‐carboxyfluorescein succinimidyl ester dilution. B cell Ig isotype switching was measured by enzyme‐linked immunospot assay.

Results

Anti–double‐stranded DNA (anti‐dsDNA) autoantibodies were preferentially secreted by a subpopulation of CD5+ B‐1 cells that expressed programmed death ligand 2 (termed L2pB1 cells). A substantial proportion of hybridoma clones generated from L2pB1 cells reacted to dsDNA. Moreover, these clones were highly cross‐reactive with other lupus‐related autoantigens. L2pB1 cells were potent antigen‐presenting cells and promoted Th17 cell differentiation in vitro. A dramatic increase of circulating L2pB1 cells in lupus‐prone BXSB mice was correlated with elevated serum titers of anti‐dsDNA antibodies. A significant number of L2pB1 cells preferentially switched to IgG1 and IgG2b when stimulated with interleukin‐21.

Conclusion

Our findings identify a novel subpopulation of B‐1 cells that is enriched for autoreactive specificities, undergoes isotype switch, manifests enhanced antigen presentation, promotes Th17 cell differentiation, and is preferentially associated with the development of lupus in a murine model. Together, these findings suggest that L2pB1 cells have the potential to initiate autoimmunity through serologic and T cell–mediated mechanisms.
Lymphopenia is a risk factor in the progression of carotid intima‐media thickness in juvenile‐onset systemic lupus erythematosus
Authors: Huang Yu‐Lin , Chung Hung‐Tao , Chang Chee‐Jen , Yeh Kuo‐Wei , Chen Li‐Chen , Huang Jing‐Long
Published: November 2009

Objective

To characterize the atherosclerotic risk factors in the progression of subclinical atherosclerosis in patients with juvenile‐onset systemic lupus erythematosus (SLE).

Methods

This was a longitudinal study of 76 patients with juvenile‐onset SLE. Carotid arteries were evaluated using ultrasonography at baseline and at followup visits at 6‐month intervals over the 6‐year study period. Clinical and laboratory parameters, disease activity, treatment, and traditional risk factors for atherosclerosis were evaluated. Data were analyzed using generalized estimating equations.

Results

The mean ± SD age of the patients at baseline was 15.01 ± 3.48 years and the mean ± SD disease duration was 2.65 ± 2.5 years. The mean ± SD duration of followup was 3.74 ± 1.24 years. The mean ± SD intima‐media thickness (IMT) of the common carotid arteries differed significantly between the patient and control (n = 38) groups (0.63 ± 0.08 mm versus 0.54 ± 0.06 mm; P < 0.001). The presence of lymphopenia at diagnosis and at baseline and higher levels of serum creatinine and C‐reactive protein at baseline were positively associated with progression of carotid IMT (P = 0.006, P = 0.043, P = 0.037, and P = 0.049, respectively). In multivariate analysis, only lymphopenia at baseline and at diagnosis were consistently associated with progression of IMT (P = 0.012 and P = 0.045, respectively).

Conclusion

In patients with juvenile‐onset SLE, some nontraditional risk factors for the progression of subclinical atherosclerosis were identified. Lymphopenia was the only independent risk factor for the progression of IMT. The pathogenic mechanisms warrant further investigation.
Local vs. global approaches to reproducing the Rey Osterrieth complex figure by children, adolescents, and adults with high‐functioning autism
Authors: Kuschner Emily S. , Bodner Kimberly E. , Minshew Nancy J.
Published: November 2009

Individuals with autism have an atypical pattern of visual processing. Various studies have provided evidence that individuals with autism perceive the details of stimuli before the gestalt, the reverse of the typical pattern of visual processing. This study used the Rey Osterreith Complex Figure (ROCF) task and an objective scoring system to examine local/global processing approaches to its reproduction in 37 individuals diagnosed with high‐functioning autism (HFA) compared to 49 age‐, IQ‐, and gender‐matched typically developing controls (TD). The sample was divided into children (aged 8–14 years) and adolescents/adults (aged 15–47 years) to assess age effects. Results showed no difference in overall performance on the ROCF between HFA and TD children. TD participants displayed improved organizational and planning skills with age and a shift to global processing approaches, but there were no differences in performance between children and adolescents/adults with HFA. There was no evidence of enhanced local processing in either HFA group. These findings suggest that HFA individuals with average IQ scores do not have the clinically demonstrable evidence of the enhanced local processing thought to reflect increased local brain connectivity in more severely autistic individuals. The deficient global processing of the HFA adults reflects dependence of performance on impaired strategic problem‐solving abilities, which has been demonstrated to result from under development of neural connectivity between visuo‐spatial and frontal brain regions in HFA adults.
Gastroschisis prevalence in Texas 1999–2003
Authors: Benjamin Bonna G. , Ethen Mary K. , Van Hook Catherine L. , Myers Candace A. , Canfield Mark A.
Published: November 2009

BACKGROUND

The worldwide prevalence of gastroschisis is increasing. Maternal age, race/ethnicity, and place of residence have been associated with increased risk.

METHODS

We obtained descriptive characteristics of mothers of infants with gastroschisis and mothers of all live births from the Texas Birth Defects Registry and Texas vital records for 1999–2003. We calculated prevalence, crude prevalence ratios, and prevalence ratios adjusted for maternal age, parity, education, race/ethnicity, and geographic entity (Mexican border proximity, urban/rural residence, health service region, and county).

RESULTS

We observed 764 cases of gastroschisis among 1,827,317 live births, for a prevalence of 4.18 per 10,000 births (95% confidence interval 3.88–4.48). Prevalence increased during 1999–2003 (p for trend <0.02). Infants of young and nulliparous mothers were at greatest risk in crude analyses. Other characteristics associated with increased risk were 12 or fewer years of education, border residence, and Hispanic ethnicity. Black mothers were at lower risk. When adjusted for maternal age, race/ethnicity, education, parity, and residence, we found that border residence, educational level, and Hispanic race/ethnicity were no longer significant, but young mothers and nulliparous mothers remained at higher risk, and blacks at reduced risk. Differences in prevalence observed between regions and counties largely disappeared when adjusted for maternal factors. No significant difference between urban and rural residence was found.

CONCLUSION

The prevalence of gastroschisis increased in Texas during 1999–2003. Black mothers were at lower risk, and Hispanic mothers were at no greater risk than whites. No differences were found between urban/rural or border/nonborder residents. Birth Defects Research (Part A) 2010. © 2009 Wiley‐Liss, Inc.
Thermodynamic Analysis of Glycerol Steam Reforming
Authors: Dieuzeide M. L. , Amadeo N.
Published: November 2009

A thermodynamic analysis of steam reforming of glycerol using the stoichiometric method has been performed. Since the aim of this work is to study product distribution and coke formation in equilibrium, two different models have been proposed: (a) CO as primary product and (b) CO2 as primary product. Moreover, substantial information regarding the behavior of the different reactions could be acquired. Product distribution at equilibrium has been investigated in a broad range of conditions: temperature (600–1200 K), water‐to‐glycerol feed molar ratio (0:1–10:1), and pressure (1–9 atm). Glycerol conversion results completely over the whole range of the mentioned conditions. Consequently, product distribution at equilibrium is determined by water gas shift (WGS) and methanation or methane steam reforming reactions. Finally, high temperatures and a high water‐to‐glycerol feed molar ratio favor hydrogen production and decrease both methane and coke.
Exploring the Concept of Aromaticity on Complexes of a Fourfold Benzannulated Cyclopentadienyl Ligand
Authors: Pammer Frank , Sun Yu , Weismann Daniel , Sitzmann Helmut , Thiel Werner R.
Published: November 2009

The ligand dibenzo[c,g]fluorenide (Dbf−), combines a cyclopentadienide ligand and 1,1′‐binaphthyl fragment in one molecule. Preliminary investigations confirmed the special electronic situation in this 6π‐electron donor by way of a series of novel transition‐metal complexes. Herein, the electron delocalization was investigated in detail by means of DFT calculations in combination with calculations on the nucleus‐independent chemical shifts (NICS). These results clearly prove that the Dbf− ion gains the largest aromatic stabilization among all benzannulated fluorenides, and there are two almost olefinic CC bonds in this structure. These bonds undergo cyclopropanation when treated with ZnEt2 and ClCH2I in a modified Simmons–Smith reaction.
Impact of Substituents Attached to N‐Heterocyclic Carbenes on the Catalytic Activity of Copper Complexes in the Reduction of Carbonyl Compounds with Triethoxysilane
Authors: Peng Jiajian , Chen Lingzhen , Xu Zheng , Hu Yingqian , Li Jiayun , Bai Ying , Qiu Huayu , Lai Guoqiao
Published: November 2009

By using functionalized imidazolium salts such as 1‐allyl‐3‐alkylimidazolium or 1‐alkyl‐3‐vinylimidazolium salts as carbene ligand precursors, the reduction of aryl ketones with triethoxysilane may be catalyzed by copper salt/imidazolium salt/KOtBu systems. The functional substituents attached to the N‐heterocyclic carbene (NHC) serve to enhance the catalytic activity. Different copper salts also have an effect on the catalytic activity, with copper(II) acetate monohydrate being superior to copper(I) chloride.
Synthesis, Structure and Growth Mechanism of Size and Shape Tunable Au/Ag Bimetallic Nanoparticles
Authors: Zheng Pengcheng , Hu Juan , Shen Guoli , Jiang Jianhui , Yu Ruqin , Liu Guokun
Published: November 2009

By simply adding ascorbic acid in advance of AgNO3, the size and shape controllable Au/Ag bimetallic nanoparticles (NP) were prepared in the traditional Au growth solution free of seed at room temperature. The size distribution of NP is well uniform with ca. 10%–15% standard deviation in diameter. By changing CTAB concentration, the size and shape of NPs are tunable. After researching the surface‐enhanced Raman spectroscopy (SERS) behavior of the prepared NPs, an enhancement factor varied from 4.3×104 to 1.1×105 was obtained for the NP centered at ca. (64±8) nm. Electrochemical cyclic voltammetric results revealed that the so formed nanoparticles were Au riched Au/Ag bimetallic NP, and this formation might be due to the disproportionation reaction of Au+ prompted by Ag+ and the under potential deposition process of Ag+ on Au.
Direct Oxidation of Benzene to Phenol by Dioxygen over Nano‐vanadium Oxide
Authors: Gao Xiaohan , LÜ Xuechuan , Xu Jie
Published: November 2009

Reducing regents, such as ascorbic acid, are needed for vanadium‐containing catalysts to catalyze the direct oxidation of benzene to phenol by dioxygen. Quadrivalent vanadium species, reduced from quinquevalent vanadium species, can activate dioxygen to produce active oxygen species, which is important for the reaction. The key step is to prepare more V4+‐containing catalysts. Here, VOX‐C16‐A was prepared in an acidic medium to produce more V4+ species. The results of XPS and XRD studies confirmed that the vanadium species in VOX‐C16‐A was mainly V4+ ions. The results of XRD and electron diffraction patterns revealed that VOX‐C16‐A consisted of tetragonal VO2 and monoclinic VO2. Morphology observations display that the VOX‐C16‐A is made of nanorod. Investigations into the performances of the catalysts showed that VOX‐C16‐A was reusable, producing a 1.9% conversion of benzene without reducing agent.
Investigation of the Anodic Behavior of Al in Room Temperature Ionic Liquid Electrolytes: BMI‐BF4, PP14‐BF4 and BMI‐BF4·PC
Authors: Wang Jixian , Yang Li , Peng Chengxin
Published: November 2009

The anodic polarization behavior of Al, Ta and Nb foil was investigated in 1‐butyl‐3‐methylimidazolium tetrafluoroborate ionic liquid (BMI‐BF4). Compared with that of Ta and Nb foil, it showed that a better passive film was formed on Al foil surface after the anodic polarization in BMI‐BF4, which could resist the potential up to 94.58 V vs. Ag+/Ag. Besides, similar anodic behavior of Al foil was observed in N‐methyl‐N‐butylpiperidinium tetrafluoroborate ionic liquid (PP14‐BF4), which indicated that the anodic polarization behavior of Al foil was independent of the cations of RTIL. In addition, the investigation of anodic polarization behavior of Al foil was carried out in the mixture electrolytes composed of BMI‐BF4·PC. Differently, two breakdown potential processes of Al foil were presented compared to pure BMI‐BF4. Further research showed that the passive film on Al foil was mainly composed of AlF3 and Al2O3 after the first breakdown potential process, while the fluoride film increased with continual anodic polarization, which improved the anodic stability of Al foil and resisted higher breakdown potential. The high breakdown potential properties of Al foil in BMI‐BF4, PP14‐BF4 and the mixture of BMI‐BF4·PC during the anodic polarization can be favored for R&D of the high performance electrochemical devices.
Modified Mesoporous Silicate MCM‐41 for Zinc Ion Adsorption: Synthesis, Characterization and Its Adsorption Behavior
Authors: Sepehrian Hamid , Waqif‐husain Syed , Rakhshanderu Farrokh , Kamel Leila
Published: November 2009

Modified MCM‐41 has been prepared by bi‐functionalization of thiol and amino functional groups onto mesoporous silicate MCM‐41. Elemental analysis (EA), thermogravimetry analysis (TGA) and FTIR techniques were used to quantify the attachment of the thiol and amino functional groups to the mesoporous silicate pore wall. Powder X‐ray diffraction (PXRD) and nitrogen adsorption techniques were used to establish the pore diameter, packing of the pores and specific surface area of the modified mesoporous silicate MCM‐41. Adsorption behavior for 18 metal ions on this sorbent has been studied and discussed. This sorbent has high affinity for zinc ions against amino‐ or thiol‐functionalized MCM‐41 sorbents.
Well Crystallized α‐GaOOH Nanocrystals Synthesized through Hydrothermal Routes and Their Properties
Authors: Zhan Baoqing , Cui Qiliang , Liu Wei , Zhang Jian , Zhan Fuxiang , Ning Jiajia , Zou Guangtian
Published: November 2009

A facile hydrothermal process involving Ga(NO3)3·H2O·NaN3 solutions led to the formation of α‐GaOOH nano‐platelets. X‐ray diffraction (XRD) pattern revealed that the synthesized samples belonged to an orthorhombic crystal structure with lattice constants a=0.4510 nm, b=0.9750 nm and c=0.2965 nm. Transmission electron microscopy (TEM) studies showed that α‐GaOOH displayed the morphologies of an eccentric platelet‐like structure with 60–120 and 200–300 nm in the short and long axes, respectively. The average thickness of products was about 70 nm through scanning electron microscopy (SEM) images. The ultraviolet absorption of the samples was at 214 nm. The prepared α‐GaOOH nano‐platelets exhibited a broad emission band from 220 to 400 nm with a maximum at 343 nm under short UV excitation of 200 nm. Fourier transform infrared (FTIR) spectrum confirmed the existence of Ga2O and Ga–OH bending modes. A possible mechanism for the formation of α‐GaOOH nano‐platelets was discussed briefly.
Controlled Synthesis of CdClOH Sub‐nanocones by Low‐temperature Solution Process and Their Transformation into CdS Hollow Sub‐nanocones
Authors: Xiong Yanlin , Peng Yin , Liu Zhengyin
Published: November 2009

Novel CdClOH sub‐nanocone crystals were successfully synthesized on a large scale by a facile solution‐based method using polymers as crystal growth modifiers. The crystals showed cone‐like morphology. Some factors affecting the morphology and size of the product, such as reaction temperature, concentrations of polyacrylamide (PAM), and pH value of the solution, were systematically studied. Experiments implied that polymer PAM played a key role in the formation of CdClOH sub‐nanocones. A possible formation mechanism of CdClOH sub‐nanocones was suggested based on nucleation‐etching process‐recrystallization in a mild aqueous solution. Furthermore, the as‐prepared CdClOH sub‐nanocones could be further transformed into CdS hollow sub‐nanocones by an anion‐exchange reaction.
Hydrothermal Syntheses, Crystal Structure and Thermal Behavior of [(CH3)2NH2]2[B5O6(OH)4]2·[HCON(CH3)2] and [NH3CH2CH2NH3]2[B14O20(OH)6]
Authors: Li Ping , Liu Zhihong
Published: November 2009

Two novel organic base templated nonmetal borates [(CH3)2NH2]2[B5O6(OH)4]2·[HCON(CH3)2] (?) and [NH3CH2CH2NH3]2[B14O20(OH)6] (II) have been synthesized under hydrothermal conditions, and characterized by elemental analyses, FT‐IR spectroscopy, X‐ray diffraction, and TG‐DTA. Their crystal structures were determined from single crystal X‐ray diffraction. The crystal structure of compound I is characterized by forming a 3D supramolecular structure with large channels along axes b and c through OH···O hydrogen‐bonding among the [B5O6(OH)4]− anions. The crystal structure of compound II is characterized by forming a 3D supramolecular structure with large channels along axis a and direction [111] through OH···O hydrogen‐bonding among the [B14O20(OH)6]4− anions. The templating organic amine cations in I and II are both obtained through in situ hydrothermal reactions, and are both located in the channels of the 3D supramolecular structure, respectively. Their thermal behavior has been also investigated.
DNA Separation by Microchip Electrophoresis Using Copolymers of Poly(vinylpyrrolidone) and Hydroxyethylcellulose
Authors: Li Gang , Ni Xiangfang , Dong Shuqing , Wang Qingjiang , He Pinggang , Fang Yuzhi
Published: November 2009

Copolymers of poly(vinylpyrrolidone) (PVP) and hydroxyethylcellulose (HEC) were synthesized, with PVP to HEC molar ratios of 3:1, 2:1 and 1:1. The copolymers were tested as separation media in DNA fragment separation analysis by microchip electrophoresis (MCE). Separation efficiency over 3.8×105 for 118 bp has been reached by using the bare channels without the additional polymer coating step. Under optimized separation conditions for longer read length DNA sequencing, the separation ability of the copolymers decreased with decreasing (PVP‐co‐HEC) molar ratio from 3:1 to 2:1 and 1:1. In comparison with (PVP‐co‐HEC) 1:1, the copolymer with (PVP‐co‐HEC) 3:1 ratio showed high separation efficiency. By using a 20 g·L−1 copolymer with (PVP‐co‐HEC) 3:1 ratio, ΦΧ174‐HaeIII digest DNA marker was successfully separated within 3 min.