bluuebunny/crossref_metadata_2025 huggingface dataset:
Recent Developments in the Application of Phosphorescent Iridium(III) Complex Systems
Authors: Ulbricht Christoph , Beyer Beatrice , Friebe Christian , Winter Andreas , Schubert Ulrich S.
Published: October 2009

The recent developments in using iridium(III) complexes as phosphorescent emitters in electroluminescent devices, such as (white) organic light‐emitting diodes and light‐emitting electrochemical cells, are discussed. Additionally, applications in the emerging fields of molecular sensors, biolabeling, and photocatalysis are briefly evaluated. The basic strategies towards charged and non‐charged iridium(III) complexes are summarized, and a wide range of assemblies is discussed. Small‐molecule‐ and polymer‐based materials are under intense investigation as emissive systems in electroluminescent devices, and special emphasis is placed on the latter with respect to synthesis, characterization, electro‐optical properties, processing technologies, and performance.
A bi‐criterion optimization approach for the design and planning of hydrogen supply chains for vehicle use
Authors: Guillén‐Gosálbez Gonzalo , Mele Fernando D. , Grossmann Ignacio E.
Published: September 2009

In this article, we address the design of hydrogen supply chains for vehicle use with economic and environmental concerns. Given a set of available technologies to produce, store, and deliver hydrogen, the problem consists of determining the optimal design of the production‐distribution network capable of satisfying a predefined hydrogen demand. The design task is formulated as a bi‐criterion mixed‐integer linear programming (MILP) problem, which simultaneously accounts for the minimization of cost and environmental impact. The environmental impact is measured through the contribution to climate change made by the hydrogen network operation. The emissions considered in the analysis are those associated with the entire life cycle of the process, and are quantified according to the principles of Life Cycle Assessment (LCA). To expedite the search of the Pareto solutions of the problem, we introduce a bi‐level algorithm that exploits its specific structure. A case study that addresses the optimal design of the hydrogen infrastructure needed to fulfill the expected hydrogen demand in Great Britain is introduced to illustrate the capabilities of the proposed approach. © 2009 American Institute of Chemical Engineers AIChE J, 2010
On the nature of Ti(IV)‐pillared layered metal hydroxides prepared from green, water‐soluble Ti‐peroxide
Authors: He Jing , Shi Huimin , Shu Xin , Li Minglin
Published: September 2009

Ti‐peroxide pillared layered double hydroxides (LDHs) have been prepared for the first time using water‐soluble Ti‐peroxide as an intercalating precursor. It is novel and alluring that the whole preparation procedure does not involve any usage of organic or chlorine‐containing hazards. Intercalated into the LDH interlayer region, Ti‐peroxide is prevented partially from condensation in the solvent evaporation. The interlayer TiO2 unit exists in triangular (η2) structure with C2ν symmetry in most cases, giving an interlayer gallery of 0.50–0.60 nm. But in the case of pH 4.0, monodentate (η1) structure is also observed, giving an interlayer gallery of 0.70 nm. All the Ti‐peroxide pillared LDHs prepared in this work show catalytic activity in the selective oxidation of thioether. The Ti‐peroxide introduced into the interlayer regions of Mg/Al LDH with a particle size of around 50–120 nm exhibits better recyclability than Ti‐peroxide gel, either in bulk or adsorbed on the exterior surface of LDH particles. © 2009 American Institute of Chemical Engineers AIChE J, 2010
An atomization model for splash plate nozzles
Authors: Sarchami Araz , Ashgriz Nasser , Tran Honghi
Published: September 2009

A model for the atomization and spray formation by splash plate nozzles is presented. This model is based on the liquid sheet formation theory due to an oblique impingement of a liquid jet on a solid surface. The continuous liquid sheet formed by the jet impingement is replaced with a set of dispersed droplets. The initial droplet sizes and velocities are determined based on theoretically predicted liquid sheet thickness and velocity. A Lagrangian spray code is used to model the spray dynamics and droplet size distribution further downstream of the nozzle. Results of this model are confirmed by the experimental data on the droplet size distribution across the spray. © 2009 American Institute of Chemical Engineers AIChE J, 2010
Neues zur Synthese von Diazoverbindungen
Authors: Maas Gerhard
Published: September 2009

Aufgrund der vielseitigen und nützlichen Folgechemie von Diazoverbindungen (R1R2CN2) ist das Interesse an dieser Substanzklasse seit Jahren ungebrochen. Dabei wird auch das bereits vorhandene Methodenrepertoire zur Herstellung von Diazoverbindungen immer wieder um neue Verfahren oder um neuartige Varianten etablierter Synthesewege ergänzt. Nicht selten tragen die neuen Synthesevorschläge der Labilität und beachtlichen chemischen Reaktivität bestimmter Typen von Diazoverbindungen Rechnung, aber auch dem Aspekt umweltfreundlicherer Methodik wurde Beachtung geschenkt.
Immunogenetic risk and protective factors for the development of L‐tryptophan–associated eosinophilia–myalgia syndrome and associated symptoms
Authors: Okada Satoshi , Kamb Mary L. , Pandey Janardan P. , Philen Rossanne M. , Love Lori A. , Miller Frederick W.
Published: September 2009

Objective

To assess L‐tryptophan (LT) dose, age, sex, and immunogenetic markers as possible risk or protective factors for the development of LT‐associated eosinophilia–myalgia syndrome (EMS) and related clinical findings.

Methods

HLA–DRB1 and DQA1 allele typing and Gm/Km phenotyping were performed on a cohort of 94 white subjects with documented LT ingestion and standardized evaluations. Multivariate analyses compared LT dose, age, sex, and alleles among groups of subjects who ingested LT and subsequently developed surveillance criteria for EMS, developed EMS or characteristic features of EMS (EMS spectrum disorder), or developed no features of EMS (unaffected).

Results

Considering all sources of LT, higher LT dose (odds ratio [OR] 1.4, 95% confidence interval [95% CI] 1.1–1.8), age >45 years (OR 3.0, 95% CI 1.0–8.8), and HLA–DRB1*03 (OR 3.9, 95% CI 1.2–15.2), DRB1*04 (OR 3.9, 95% CI 1.1–16.4), and DQA1*0601 (OR 13.7, 95% CI 1.3–1.8) were risk factors for the development of EMS, whereas DRB1*07 (OR 0.12, 95% CI 0.02–0.48) and DQA1*0501 (OR 0.23, 95% CI 0.05–0.85) were protective. Similar risk and protective factors were seen for developing EMS following ingestion of implicated LT, except that DRB1*03 was not a risk factor and DQA1*0201 was an additional protective factor. EMS spectrum disorder also showed similar findings, but with DRB1*04 being a risk factor and DRB1*07 and DQA1*0201 being protective. There were no differences in sex distribution, Gm/Km allotypes, or Gm/Km phenotypes among any groups.

Conclusion

In addition to the xenobiotic dose and subject age, polymorphisms in immune response genes may underlie the development of certain xenobiotic‐induced immune‐mediated disorders, and these findings may have implications for future related epidemics.
Prevalence and incidence of Wegener's granulomatosis in the UK general practice research database
Authors: Watts Richard A. , Al‐Taiar Abdullah , Scott David G. I. , Macgregor Alex J.
Published: September 2009

Objective

Wegener's granulomatosis (WG) is a systemic vasculitis of unknown etiology. The UK General Practice Research Database (GPRD) contains the complete primary care records of ∼3.6 million people. There are no data on the incidence and prevalence of WG from primary care. The aim of the study was to estimate the incidence and prevalence of WG in the GPRD population.

Methods

We identified all patients who had a first diagnosis of WG during 1990–2005, using Oxford Information System and Read codes. The diagnosis was verified by review of a randomly selected sample of 35 records that had identifying data removed. The annual incidence was calculated as the number of incident cases divided by the total person‐years.

Results

A total of 295 patients (51.2% male) with a first diagnosis of WG were identified during 1990–2005. The median age was 59 years (interquartile range 47–70 years). The overall annual incidence of WG was 8.4 per million (95% confidence interval [95% CI] 7.5–9.4). The annual rate in women and men was 8.1 per million (95% CI 6.8–9.6), and 8.8 per million (95% CI 7.4–10.3), respectively. The incidence was stable throughout the study period. There was an increase in the annual prevalence from 28.8 per million in 1990 to 64.8 per million in 2005. The diagnosis was verified in 28 of 31 available case records.

Conclusion

This is the first study of the incidence and prevalence of WG in a database from a primary care population. The results are similar to previous studies from secondary and tertiary care and suggest that these studies are representative of the general population. The increasing prevalence with a constant incidence suggests that survival is improving with modern treatment protocols.
Heritability of spinal pain and consequences of spinal pain: A comprehensive genetic epidemiologic analysis using a population‐based sample of 15,328 twins ages 20–71 years
Authors: Hartvigsen Jan , Nielsen Jan , Kyvik Kirsten OHM , Fejer Rene , Vach Werner , Iachine Ivan , Leboeuf‐Yde Charlotte
Published: September 2009

Objective

To assess the relative contribution of genetic and environmental factors to different definitions of spinal pain and consequences of spinal pain.

Methods

The Danish Twin Registry contains detailed survey information on spinal pain and its consequences in twins ages 20–71 years. A classic genetic epidemiologic analysis was performed in order to establish heritability for a number of phenotypes, including location of pain, radiation of pain in the extremities or chest, pain duration, and combinations of pain in >1 spinal area. Consequences included reduced physical activity, sick leave, care seeking, change of work, and disability pension. The analysis included a biometric analysis based on the effect of shared genetic and common environmental factors. Furthermore, a bivariate twin model was fitted to identify genetic and environmental correlations.

Results

Altogether, data on 15,328 twin individuals (44% monozygotic and 56% dizygotic) from complete twin pairs were included. Genetic susceptibility explained ∼38% of lumbar pain, 32% of thoracic pain, and 39% of neck pain. For patterns of pain, estimates were 7% for lumbar/thoracic, 24% for lumbar/cervical, 0% for thoracic/cervical, and 35% for pain in all 3 areas. Moderate to high genetic correlations indicated a common genetic basis for many spinal pain syndromes. In general, heritability was higher for women, and only a minor age effect was seen.

Conclusion

Heritability estimates for pain in different spinal regions are quite similar and there is a moderate to high genetic correlation between the phenotypes. This may indicate a common genetic basis for a high proportion of spinal pain.
HLA–B51/B5 and the risk of Behçet's disease: A systematic review and meta‐analysis of case–control genetic association studies
Authors: de Menthon Mathilde , LaValley Michael P. , Maldini Carla , Guillevin Loïc , Mahr Alfred
Published: September 2009

Objective

To quantify by meta‐analysis the genetic effect of the HLA–B5 or HLA–B51 (HLA–B51/B5) allele on the risk of developing Behçet's disease (BD) and to look for potential effect modifiers.

Methods

Relevant studies were identified using the PubMed Medline database and manual searches of the literature. Pooled odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated by using the random‐effects model. Subgroup meta‐analyses and meta‐regression analyses were undertaken to investigate the effects of selected study‐level parameters on the pooled OR. Heterogeneity was assessed using the I2 statistic. Pooled results were used to calculate population‐attributable risks (PAR) for BD in relationship to HLA–B51/B5.

Results

A total of 4,800 patients with BD and 16,289 controls from 78 independent studies (published 1975–2007) were selected. The pooled OR of HLA–B51/B5 allele carriers to develop BD compared with noncarriers was 5.78 (95% CI 5.00–6.67), with moderate between‐study heterogeneity (I2 = 61%). The subgroup analyses stratifying studies by geographic locations (Eastern Asia, Middle East/North Africa, Southern Europe, Northern/Eastern Europe) yielded consistent OR ranges (5.31–7.20), with I2 ranges of 52–70%. Univariate random‐effects meta‐regression indicated the percentage of male BD cases (P = 0.008) as a source of heterogeneity. The PAR within the various geographic areas were estimated at 32–52%.

Conclusion

The strength of the association between BD and HLA–B51/B5, and its consistency across populations of various ethnicities, lends further support to this allele being a primary and causal risk determinant for BD. Variations according to sex support an interaction of this allele with BD characteristics.
Squatting, sitting on the floor, or cycling: Are life‐long daily activities risk factors for clinical knee osteoarthritis? Stage III results of a community‐based study
Authors: Dahaghin S. , Tehrani‐Banihashemi S. A. , Faezi S. T. , Jamshidi A. R. , Davatchi F.
Published: September 2009

Objective

To evaluate the association between occupations, sports, life‐long daily activities, and knee osteoarthritis.

Methods

In this case–control study, we randomly recruited 480 subjects with knee osteoarthritis, who had participated in the first stage of a community‐based study in Tehran, and compared them with 490 controls. A questionnaire was used to record all occupations, sports, and the details of 10 daily activities. The mean ± SD hours/day spent on these activities were calculated and compared using the lightest activity as reference. Generalized estimation equation was used with each knee as the unit of analysis.

Results

The mean ± SD age and percentage of female distribution was 57 ± 12 years, 69.8% women for cases, and 46.8 ± 15 years, 64.1% women for controls. After adjusting for age, sex, and body mass index, 2 activities were risk factors for knee osteoarthritis: prolonged squatting (odds ratio [OR] 1.51, 95% confidence interval [95% CI] 1.12–2.04) and cycling (OR 2.06, 95% CI 1.23–3.45). Knee‐bending had borderline significance (OR 1.98, 95% CI 0.98–3.99). Carrying loads (OR 1.24, 95% CI 0.87–1.76) or climbing stairs (OR 0.99, 95% CI 0.69–1.42) showed no extra risk for knee osteoarthritis. Prolonged standing, sitting on the floor, and walking up/downhill were not risks for knee osteoarthritis. Housewives were at greater risk (borderline‐significant) of developing knee osteoarthritis (OR 1.68, 95% CI 0.93–3.03) than women whose main occupation was outside the home. Other types of jobs and sports did not show an extra risk of knee osteoarthritis.

Conclusion

Our findings support the role of lifestyle in the pathogenesis of knee osteoarthritis for squatting and cycling. Education on preventable risk factors should be considered in order to ensure people use knee joints appropriately and avoid overuse.
25‐hydroxyvitamin D and cardiovascular risk factors in women with systemic lupus erythematosus
Authors: Wu Peggy W. , Rhew Elisa Y. , Dyer Alan R. , Dunlop Dorothy D. , Langman Craig B. , Price Heather , Sutton‐Tyrrell Kim , McPherson David D. , Edmundowicz Daniel , Kondos George T. , Ramsey‐Goldman Rosalind
Published: September 2009

Objective

Low serum levels of 25‐hydroxyvitamin D (25[OH]D; vitamin D) are associated with a higher frequency of cardiovascular disease and risk factors in the general population. Vitamin D deficiency has also been noted in systemic lupus erythematosus (SLE). The objective of this study was to evaluate the associations of serum 25(OH)D levels with cardiovascular risk factors in women with SLE.

Methods

Data collected in 181 women with SLE included demographics, SLE activity and damage assessments, cardiovascular risk factors, medications, and laboratory assessments of inflammatory markers and 25(OH)D levels. Multiple linear and logistic regressions were used to estimate the association of 25(OH)D levels with cardiovascular risk factors.

Results

The mean age and disease duration were 43.2 and 11.9 years, respectively. The mean 25(OH)D level was 27.1 ng/ml and 62.2% had 25(OH)D levels <30 ng/ml. In unadjusted analyses, lower 25(OH)D levels were significantly associated with higher diastolic blood pressure, low‐density lipoprotein cholesterol, lipoprotein(a), body mass index (BMI), and fibrinogen levels, as well as self‐reported hypertension and diabetes mellitus. Lower 25(OH)D levels were also significantly associated with higher SLE disease activity and damage scores. After adjustment for age, seasonal variation, and race/ethnicity, lower 25(OH)D levels were also significantly related to higher fasting serum glucose. With further adjustment for BMI, associations between 25(OH)D and cardiovascular risk factors were no longer significant.

Conclusion

This study demonstrates that vitamin D levels are low in women with SLE and significant associations exist with selected cardiovascular risk factors, although most of these associations can be explained by BMI.
Normalization of A2Aand A3adenosine receptor up‐regulation in rheumatoid arthritis patients by treatment with anti–tumor necrosis factor α but not methotrexate
Authors: Varani Katia , Massara Alfonso , Vincenzi Fabrizio , Tosi Alice , Padovan Melissa , Trotta Francesco , Borea Pier Andrea
Published: September 2009

Objective

To investigate A1, A2A, A2B, and A3adenosine receptors in lymphocytes and neutrophils from patients with early rheumatoid arthritis (ERA) as well as from RA patients treated with methotrexate (MTX) or anti–tumor necrosis factor α (anti‐TNFα), as compared with those in age‐matched healthy controls, and to examine correlations between the status and functionality of adenosine receptors and TNFα release and NF‐κB activation.

Methods

Adenosine receptors were analyzed by saturation binding assays and Western blot analyses. We investigated the potency of typical A2Aand A3agonists in the production of cAMP in control subjects, ERA patients, and RA patients treated with MTX or anti‐TNFα. In a separate cohort of RA patients, TNFα release and NF‐κB activation were evaluated in plasma and nuclear extracts, respectively.

Results

In ERA patients, we found a high density and altered functionality of A2Aand A3receptors. The binding and functional parameters of A2Aand A3receptors normalized after anti‐TNFα, but not MTX, treatment. TNFα release was increased in ERA patients and in MTX‐treated RA patients, whereas in anti‐TNFα–treated RA patients, release was comparable to that in the controls. NF‐κB activation was elevated in ERA patients and in MTX‐treated RA patients. Anti‐TNFα treatment mediated decreased levels of NF‐κB activation.

Conclusion

A2Aand A3receptor up‐regulation in ERA patients and in MTX‐treated RA patients was associated with high levels of TNFα and NF‐κB activation. Treatment with anti‐TNFα normalized A2Aand A3receptor expression and functionality. This new evidence of A2Aand A3receptor involvement opens the possibility of exploiting their potential role in human diseases characterized by a marked inflammatory component.
IgG4‐related systemic disease and lymphoplasmacytic aortitis
Authors: Stone John H. , Khosroshahi Arezou , Hilgenberg Alan , Spooner Amy , Isselbacher Eric M. , Stone James R.
Published: September 2009

We describe herein a patient who developed a dissection of the ascending aorta in the setting of IgG4‐related systemic disease, linking IgG4‐related systemic disease with a newly‐recognized subset of noninfectious aortitis. At the time of aortic surgery, a transmural lymphoplasmacytic infiltrate was detected in the patient's aorta, with a principal focus of inflammation within the media. Immunohistochemical studies demonstrated that >50% of the plasma cells in the lesion stained for IgG4. By in situ hybridization, the plasma cells showed polytypic staining for kappa and lambda light chains, consistent with a polyclonal plasma cell infiltrate. Serologic evaluation revealed that the patient's IgG4 levels were elevated nearly 10‐fold. Four years before aortic surgery, the patient had undergone a mediastinal lymph node biopsy. Reexamination of the lymph node revealed features consistent with IgG4‐related systemic disease, which had not been recognized at the time of the original biopsy. Glucocorticoid therapy for the IgG4‐related systemic disease yielded a prompt response. Recognition that IgG4‐related systemic disease can involve the ascending as well as the descending abdominal aorta indicates the need for a change in the way idiopathic aortitis is regarded. This case offers new potential considerations for short‐ and long‐term management of noninfectious aortitis, because of the frequent good response of IgG4‐related systemic disease to glucocorticoid treatment without additional therapy. Treatment of the aortitis may prevent progression of the IgG4‐related systemic disease to involvement of other organs. IgG4‐related systemic disease should be considered in all patients with aortitis judged to be of unknown etiology.
Functional characterization of TRPV4 as an osmotically sensitive ion channel in porcine articular chondrocytes
Authors: Phan Mimi N. , Leddy Holly A. , Votta Bartholomew J. , Kumar Sanjay , Levy Dana S. , Lipshutz David B. , Lee Suk Hee , Liedtke Wolfgang , Guilak Farshid
Published: September 2009

Objective

Transient receptor potential vanilloid 4 (TRPV4) is a Ca2+‐permeable channel that can be gated by tonicity (osmolarity) and mechanical stimuli. Chondrocytes, the cells in cartilage, respond to their osmotic and mechanical environments; however, the molecular basis of this signal transduction is not fully understood. This study was undertaken to demonstrate the presence and functionality of TRPV4 in chondrocytes.

Methods

TRPV4 protein expression was measured by immunolabeling and Western blotting. In response to TRPV4 agonist/antagonists, osmotic stress, and interleukin‐1 (IL‐1), changes in Ca2+ signaling, cell volume, and prostaglandin E2 (PGE2) production were measured in porcine chondrocytes using fluorescence microscopy, light microscopy, or immunoassay, respectively.

Results

TRPV4 was expressed abundantly at the RNA and protein levels. Exposure to 4α‐phorbol 12,13‐didecanoate (4αPDD), a TRPV4 activator, caused Ca2+ signaling in chondrocytes, which was blocked by the selective TRPV4 antagonist, GSK205. Blocking TRPV4 diminished the chondrocytes' response to hypo‐osmotic stress, reducing the fraction of Ca2+ responsive cells, the regulatory volume decrease, and PGE2 production. Ca2+ signaling was inhibited by removal of extracellular Ca2+ or depletion of intracellular stores. Specific activation of TRPV4 restored the defective regulatory volume decrease caused by IL‐1. Chemical disruption of the primary cilium eliminated Ca2+ signaling in response to either 4αPDD or hypo‐osmotic stress.

Conclusion

Our findings indicate that TRPV4 is present in articular chondrocytes, and chondrocyte response to hypo‐osmotic stress is mediated by this channel, which involves both an extracellular Ca2+ and intracellular Ca2+ release. TRPV4 may also be involved in modulating the production or influence of proinflammatory molecules in response to osmotic stress.
The impact of anterior cruciate ligament injury on lubricin metabolism and the effect of inhibiting tumor necrosis factor α on chondroprotection in an animal model
Authors: Elsaid K. A. , Machan J. T. , Waller K. , Fleming B. C. , Jay G. D.
Published: September 2009

Objective

To examine the effects of anterior cruciate ligament transection (ACLT) in a rat model on lubricin metabolism and its relationship to markers of inflammation and cartilage damage, and to determine whether blocking the metabolic effects of tumor necrosis factor α (TNFα) by etanercept increases the chondroprotection provided by lubricin.

Methods

Unilateral ACLT was performed in Lewis rats. Levels of lubricin, TNFα, interleukin‐1β (IL‐1β), and sulfated glycosaminoglycans (sGAG) in synovial fluid (SF) lavage specimens and synovial tissue lubricin gene expression were evaluated at 1 week and 4 weeks following ACLT. Histologic evaluation of articular cartilage included staining with lubricin‐specific monoclonal antibody 9G3 and Safranin O. The percentage of lubricin staining on the surface of articular cartilage in weight‐bearing areas was estimated by digital imaging. Blocking of TNFα was performed using etanercept, which was administered subcutaneously at a dose of 0.5 mg/kg around the ACL‐transected joints, using different dosing strategies. The ACL‐transected and contralateral joints of these rats were harvested 4 weeks following surgery.

Results

Four weeks following ACLT, SF lubricin concentrations and the percentage of cartilage surface lubricin staining were significantly lower in the injured joints compared with the contralateral joints. A significant decrease in synovial tissue lubricin gene expression was associated with elevated TNFα and IL‐1β concentrations in SF lavage samples. With all of the etanercept treatment strategies, blocking of TNFα significantly increased the amount of lubricin bound to cartilage, coupled with a significant decrease in sGAG release. However, changes in the concentrations of lubricin in SF were variable.

Conclusion

Blocking TNFα resulted in a chondroprotective effect, exemplified by increased lubricin deposition on articular cartilage and a decrease in sGAG release from articular cartilage in an animal model of posttraumatic arthritis.
Interferon‐regulated chemokines as biomarkers of systemic lupus erythematosus disease activity: A validation study
Authors: Bauer Jason W. , Petri Michelle , Batliwalla Franak M. , Koeuth Thearith , Wilson Joseph , Slattery Catherine , Panoskaltsis‐Mortari Angela , Gregersen Peter K. , Behrens Timothy W. , Baechler Emily C.
Published: September 2009

Objective

Systemic lupus erythematosus (SLE) is a complex autoimmune disease characterized by unpredictable flares of disease activity and irreversible damage to multiple organ systems. An earlier study showed that SLE patients carrying an interferon (IFN) gene expression signature in blood have elevated serum levels of IFN‐regulated chemokines. These chemokines were associated with more‐severe and active disease and showed promise as SLE disease activity biomarkers. This study was designed to validate IFN‐regulated chemokines as biomarkers of SLE disease activity in 267 SLE patients followed up longitudinally.

Methods

To validate the potential utility of serum chemokine levels as biomarkers of disease activity, we measured serum levels of CXCL10 (IFNγ‐inducible 10‐kd protein), CCL2 (monocyte chemotactic protein 1), and CCL19 (macrophage inflammatory protein 3β) in an independent cohort of 267 SLE patients followed up longitudinally over 1 year (1,166 total clinic visits).

Results

Serum chemokine levels correlated with lupus activity at the current visit (P = 2 × 10−10), rising at the time of SLE flare (P = 2 × 10−3) and decreasing as disease remitted (P = 1 × 10−3); they also performed better than the currently available laboratory tests. Chemokine levels measured at a single baseline visit in patients with a Systemic Lupus Erythematosus Disease Activity Index of ≤4 were predictive of lupus flare over the ensuing year (P = 1 × 10−4).

Conclusion

Monitoring serum chemokine levels in SLE may improve the assessment of current disease activity, the prediction of future disease flares, and the overall clinical decision‐making.
Association of immunoglobulin‐like transcript 6 deficiency with Sjögren's syndrome
Authors: Kabalak G. , Dobberstein S. B. , Matthias T. , Reuter S. , The Y.‐H. , Dörner T. , Schmidt R. E. , Witte T.
Published: September 2009

Objective

The immunoglobulin‐like transcript (ILT) family is located in chromosomal region 19q13 and consists of a group of activating and inhibitory receptors. The ILT receptors are expressed on antigen‐presenting cells (macrophages, dendritic cells, B lymphocytes), as well as on T cells and natural killer cells. ILT2 and ILT4 play a role in tolerance induction, and ILT3 has been shown to induce Treg cells. A homozygous deletion of ILT6 has been shown to be associated with multiple sclerosis. Since ILT6 may be a modulator of the immune system, we undertook this study to examine the association of ILT6 deficiency with Sjögren's syndrome (SS).

Methods

We genotyped 149 patients with SS and 749 healthy controls, using polymerase chain reaction to test for the presence or absence of ILT6.

Results

Homozygous ILT6 deficiency was detected in 8% of SS patients and in only 3% of controls.

Conclusion

Our findings indicate that ILT6 deficiency may be a genetic risk factor for SS.
Association of functional outcome with both personal‐ and area‐level socioeconomic inequalities in patients with inflammatory polyarthritis
Authors: Harrison Mark J. , Farragher Tracey M. , Clarke Alexandra M. , Manning Stephanie C. , Bunn Diane K. , Symmons Deborah P. M.
Published: September 2009

Objective

To describe the relationship between baseline area‐ and person‐level social inequalities and functional disability at 3 years in patients with early inflammatory polyarthritis (IP).

Methods

A total of 1,393 patients with new‐onset IP were recruited and allocated an Index of Multiple Deprivation (IMD) 2004 score based on their area of residence, and a social class based on baseline self‐reported occupation. Differences in the Health Assessment Questionnaire (HAQ) score at baseline and 3 years by IMD or social class were tested. The mean 3‐year change in HAQ score was compared by IMD and social class, and interactions between these measures examined.

Results

Patients from more deprived areas had poorer 3‐year HAQ outcome than those from less deprived areas (P = 0.019, adjusted for baseline HAQ score, age, sex, and symptom duration). The mean difference in HAQ change was most notable between the most deprived (IMD4) and least deprived areas (IMD1) (0.22; 95% confidence interval [95% CI] 0.11, 0.34). There was also a significant difference in HAQ score change between patients of the highest (SCI and II) and lowest social class (SCIV and V) (0.11; 95% CI 0.02, 0.20). For the mean (95% CI) 3‐year change in HAQ score, a significant interaction exists between IMD score and social class and their association with HAQ scores (P = 0.001) to modify outcome: IMD1/SC I and II −0.23 (95% CI −0.40, −0.06) versus IMD 4/SC IV and V 0.15 (95% CI −0.05, 0.34).

Conclusion

Person‐ and area‐level inequalities combine to modify outcome for rheumatoid arthritis. A person's social circumstance and residential environment have independent effects on outcome and are not just alternative measures of the same exposure.
The melanocortin system in articular chondrocytes: Melanocortin receptors, pro‐opiomelanocortin, precursor proteases, and a regulatory effect of α‐melanocyte–stimulating hormone on proinflammatory cytokines and extracellular matrix components
Authors: Grässel Susanne , Opolka Alfred , Anders Sven , Straub Rainer H. , Grifka Joachim , Luger Thomas A. , Böhm Markus
Published: September 2009

Objective

The pro‐opiomelanocortin (POMC)–derived neuropeptide α‐melanocyte–stimulating hormone (α‐MSH) mediates its effects via melanocortin (MC) receptors. This study was carried out to investigate the expression patterns of the MC system and the effects of α‐MSH in human articular chondrocytes.

Methods

Articular chondrocytes established from human osteoarthritic joint cartilage were analyzed by reverse transcription–polymerase chain reaction (RT‐PCR) and Western blotting for the expression of MC receptors, POMC, and prohormone convertases (PCs). MC‐1 receptor (MC‐1R) expression in articular cartilage was further studied by immunohistochemistry. Ca2+ and cAMP assays were used to monitor α‐MSH signaling, while studies of α‐MSH function were performed in cultures with chondrocyte micromass pellets stimulated with α‐MSH. Expression of cytokines and extracellular matrix (ECM) components was determined by real‐time RT‐PCR, Western immunoblotting, and enzyme‐linked immunosorbent assays.

Results

MC‐1R expression was detected in articular chondrocytes in vitro and in articular cartilage in situ. In addition, expression of transcripts for MC‐2R, MC‐5R, POMC, and PCs was detected in articular chondrocytes. Stimulation with α‐MSH increased the levels of intracellular cAMP, but not Ca2+, in chondrocytes. Both messenger RNA and protein expression of various proinflammatory cytokines, collagens, matrix metalloproteinases (MMPs), and SOX9 was modulated by α‐MSH.

Conclusion

Human articular chondrocytes are target cells for α‐MSH. The effects of α‐MSH on expression of cytokines and MMPs suggest that this neuropeptide plays a role in inflammatory and degenerative processes in cartilage. It is conceivable that inflammatory reactions can be mitigated by the induction of endogenous MCs or administration of α‐MSH to the affected joints. The induction pattern of regulatory and structural ECM components such as collagens as well as SOX9 and anabolic and catabolic cytokines points to a function of α‐MSH as a trophic factor in skeletal development during endochondral ossification rather than as a factor in homeostasis of permanent cartilage.
Continuous occurrence of both insufficient neovascularization and elevated vascular permeability in rabbit proximal femur during inadequate repair of steroid‐associated osteonecrotic lesions
Authors: Zhang Ge , Sheng Hui , He Yi‐Xin , Xie Xin‐Hui , Wang Yi‐Xiang , Lee Kwong‐Man , Yeung Ka‐Wai , Li Zi‐Rong , He Wei , Griffith James F. , Leung Kwok‐Sui , Qin Ling
Published: September 2009

Objective

To examine the features of the intraosseous vasculature, the size of the marrow stem cell pool (MSCP), and expression of vascular endothelial growth factor A (VEGF) during inadequate repair of steroid‐associated osteonecrotic lesions in rabbits.

Methods

Steroid‐associated osteonecrosis was induced in male rabbits. At 0, 1, 2, 4, and 6 weeks postinduction, vascularization and permeability indices were quantified by dynamic magnetic resonance imaging (MRI). In addition, the size of the MSCP in the hematopoietic and mesenchymal compartments was determined, and marrow mononuclear cells expressing specific surface markers for endothelial progenitor cells or periendothelial mural precursor cells were counted. At various time points after the rabbits were killed, the proximal femora were dissected to examine the intraosseous vasculature by angiography, histomorphometry, and ultramorphology. In addition, osteonecrotic lesion repair and marrow VEGF expression were evaluated.

Results

Lesion formation without repair was observed at 2 weeks after induction of steroid‐associated osteonecrosis. Rabbits displaying destructive repair (DR+) and those displaying reparative osteogenesis (DR−) from 4 weeks to 6 weeks postinduction were identified. From week 2 to week 6, the vascularization index was significantly lower in DR+ rabbits compared with DR− rabbits, whereas the permeability index was significantly higher in DR+ rabbits compared with DR− rabbits. The features of the intraosseous vasculature determined by angiography, histomorphometry, and ultramorphology were consistent with those determined by dynamic MRI. The MSCP size and number of marrow mononuclear cells expressing specific surface markers were all significantly lower in DR+ rabbits than in DR− rabbits from week 1 to week 6. The increased VEGF expression at 2 weeks was maintained through week 6 in DR+ rabbits, whereas VEGF expression decreased in DR− rabbits from week 2 to week 6.

Conclusion

Continuous occurrence of both insufficient neovascularization and elevated vascular permeability is accompanied by a continuously low‐ level MSCP and uncontrolled VEGF expression during inadequate repair of steroid‐associated osteonecrotic lesions.
Elevated insular glutamate in fibromyalgia is associated with experimental pain
Authors: Harris Richard E. , Sundgren Pia C. , Craig A. D. , Kirshenbaum Eric , Sen Ananda , Napadow Vitaly , Clauw Daniel J.
Published: September 2009

Objective

Central pain augmentation resulting from enhanced excitatory and/or decreased inhibitory neurotransmission is a proposed mechanism underlying the pathophysiology of functional pain syndromes such as fibromyalgia (FM). Multiple functional magnetic resonance imaging studies implicate the insula as a region of heightened neuronal activity in this condition. Since glutamate (Glu) is a major cortical excitatory neurotransmitter that functions in pain neurotransmission, we undertook this study to test our hypothesis that increased levels of insular Glu would be present in FM patients and that the concentration of this molecule would be correlated with pain report.

Methods

Nineteen FM patients and 14 age‐ and sex‐matched pain‐free controls underwent pressure pain testing and a proton magnetic resonance spectroscopy session in which the right anterior insula and right posterior insula were examined at rest.

Results

Compared with healthy controls, FM patients had significantly higher levels of Glu (mean ± SD 8.09 ± 0.72 arbitrary institutional units versus 6.86 ± 1.29 arbitrary institutional units; P = 0.009) and combined glutamine and Glu (i.e., Glx) (mean ± SD 12.38 ± 0.94 arbitrary institutional units versus 10.59 ± 1.48 arbitrary institutional units; P = 0.001) within the right posterior insula. No significant differences between groups were detected in any of the other major metabolites within this region (P > 0.05 for all comparisons), and no group differences were detected for any metabolite within the right anterior insula (P > 0.11 for all comparisons). Within the right posterior insula, higher levels of Glu and Glx were associated with lower pressure pain thresholds across both groups for medium pain (for Glu, r = −0.43, P = 0.012; for Glx, r = −0.50, P = 0.003).

Conclusion

Enhanced glutamatergic neurotransmission resulting from higher concentrations of Glu within the posterior insula may play a role in the pathophysiology of FM and other central pain augmentation syndromes.
Prevalence of and screening for serious spinal pathology in patients presenting to primary care settings with acute low back pain
Authors: Henschke Nicholas , Maher Christopher G. , Refshauge Kathryn M. , Herbert Robert D. , Cumming Robert G. , Bleasel Jane , York John , Das Anurina , McAuley James H.
Published: September 2009

Objective

To determine the prevalence of serious pathology in patients presenting to primary care settings with acute low back pain, and to evaluate the diagnostic accuracy of recommended “red flag” screening questions.

Methods

An inception cohort of 1,172 consecutive patients receiving primary care for acute low back pain was recruited from primary care clinics in Sydney, Australia. At the initial consultation, clinicians recorded responses to 25 red flag questions and then provided an initial diagnosis. The reference standard was a 12‐month followup supplemented with a specialist review of a random subsample of participants.

Results

There were 11 cases (0.9%) of serious pathology, including 8 cases of fracture. Despite the low prevalence of serious pathology, most patients (80.4%) had at least 1 red flag (median 2, interquartile range 1–3). Only 3 of the red flags for fracture recommended for use in clinical guidelines were informative: prolonged use of corticosteroids, age >70 years, and significant trauma. Clinicians identified 5 of the 11 cases of serious pathology at the initial consultation and made 6 false‐positive diagnoses. The status of a diagnostic prediction rule containing 4 features (female sex, age >70 years, significant trauma, and prolonged use of corticosteroids) was moderately associated with the presence of fracture (the area under the curve for the rule score was 0.834 [95% confidence interval 0.654–1.014]; P = 0.001).

Conclusion

In patients presenting to a primary care provider with back pain, previously undiagnosed serious pathology is rare. The most common serious pathology observed was vertebral fracture. Approximately half of the cases of serious pathology were identified at the initial consultation. Some red flags have very high false‐positive rates, indicating that, when used in isolation, they have little diagnostic value in the primary care setting.
Estrone/17β‐estradiol conversion to, and tumor necrosis factor inhibition by, estrogen metabolites in synovial cells of patients with rheumatoid arthritis and patients with osteoarthritis
Authors: Schmidt Martin , Hartung Regina , Capellino Silvia , Cutolo Maurizio , Pfeifer‐Leeg Antje , Straub Rainer H.
Published: September 2009

Objective

The role of estrogens in rheumatoid arthritis (RA) is debated since both proinflammatory and antiinflammatory effects have been reported. Important evidence of the dual role of estrogens is conversion to various proinflammatory or antiinflammatory metabolites. This study was undertaken to examine the downstream conversion of estrogens in synovial cells from patients with RA or osteoarthritis (OA).

Methods

We studied serum levels of estrone, estrone sulfate, and estrone sulfate membrane transporters, intracellular interconversion of estrone and 17β‐estradiol, and conversion of estrone/17β‐estradiol to various estrogen metabolites in RA and OA synovial cells. The effect of estrogen metabolites on tumor necrosis factor (TNF) secretion was also studied in RA and OA synovial cells.

Results

Serum levels of estrone sulfate were similar in healthy controls and RA patients. Estrone sulfate transporters were present in synovial tissue. Interconversion of estrone and 17β‐estradiol and the expression of converting enzymes of the cytochrome P450 family were similar in RA and OA cells. Using estrone and 17β‐estradiol as substrates, RA and OA synovial cells produced 16α‐, 4‐, and 2‐hydroxylated estrogens and their 4‐ and 2‐methylation products. The levels of 16α‐hydroxylated estrone/17β‐estradiol (16αOH‐estrone/16αOH‐17β‐estradiol) were higher than the levels of all other estrogen metabolites. RA synovial cells produced more 16αOH‐estrone than did OA synovial cells. Importantly, the 16αOH estrogens did not inhibit TNF secretion, whereas all other estrogen metabolites had marked inhibitory effects.

Conclusion

Our findings indicate that precursor estrogens are converted to proinflammatory metabolites, particularly in RA synovial cells. RA synovial cells mainly produce the proproliferative 16αOH‐estrone, which, in addition to 16αOH‐17β‐estradiol, is one of the only 2 estrogens studied that does not inhibit TNF secretion. A preponderance of 16α‐hydroxylated estrogens is an unfavorable sign in synovial inflammation.
Soluble neuropilin‐2, a nerve repellent receptor, is increased in rheumatoid arthritis synovium and aggravates sympathetic fiber repulsion and arthritis
Authors: Fassold Alexander , Falk Werner , Anders Sven , Hirsch Thomas , Mirsky Vladimir M. , Straub Rainer H.
Published: September 2009

Objective

In inflammatory lesions, sympathetic nerve fibers disappear soon after the start of inflammation. We identified sympathetic nerve repellents as possible causal agents in rheumatoid arthritis (RA). On nerve terminals, repellent factors bind to neuropilin‐2 and its coreceptor. The aim of this study was to investigate the role of neuropilin‐2 in the synovial tissue of patients with RA and patients with osteoarthritis (OA) and in experimental arthritis.

Methods

The density of neuropilin‐2–positive fibers and cells positive for semaphorin 3F (a sympathetic repellent) was investigated using immunofluorescence staining. Enzyme‐linked immunosorbent assay was used to detect soluble neuropilin‐2 in body fluids from patients with RA and patients with OA. An axon outgrowth assay and a neuropilin‐2 Fc fusion construct (neuropilin‐2Fc) were used to investigate semaphorin 3F–induced sympathetic nerve repulsion. In an animal model of type II collagen–induced arthritis, soluble neuropilin‐2Fc was studied in vivo.

Results

The synovial density of neuropilin‐2–positive sympathetic nerve fibers was lower in RA than in OA, but the density of cells positive for semaphorin 3F was similar. In synovial fluid, the level of soluble neuropilin‐2 was markedly higher in RA compared with OA. Mouse sympathetic ganglia served as an excellent model with which to study semaphorin 3F–induced nerve fiber repulsion. Neuropilin‐2 and its coreceptor were present on sympathetic neurons, and semaphorin 3F bound to neuropilin‐2Fc (binding constant 96 nmoles/liter). Semaphorin 3F dose‐dependently increased sympathetic nerve fiber repulsion (at a 50% maximum response concentration of 160–210 nmoles/liter). In contrast to our expectations, soluble neuropilin‐2Fc did not inhibit repulsion but increased the repellent effect of semaphorin 3F. In experimental arthritis, therapy with neuropilin‐2Fc aggravated arthritis.

Conclusion

Soluble neuropilin‐2 has no antirepellent activity but aggravates sympathetic nerve fiber repulsion and arthritis. Increased shedding of neuropilin‐2 is probably an unfavorable sign in RA.
Reversible Mechanical Induction of Optical Activity in Solutions of Soft‐Matter Nanophases
Authors: Arteaga Oriol , Escudero Carlos , Oncins Gerard , El‐Hachemi Zoubir , Llorens Joan , Crusats Joaquim , Canillas Adolf , Ribó Josep M.
Published: September 2009

Nanophases of J‐aggregates of several achiral amphiphilic porphyrins, which have thin long acicular shapes (nanoribbons), show the immediate and reversible formation of a stationary mechano‐chiral state in the solution by vortex stirring, as detected by their circular dichroic signals measured by 2‐modulator generallized ellipsometry. The results suggest that when a macroscopic chiral force creates supramolecular chirality, it also creates an enantiomeric excess of screw distortions, which may be detected by their excitonic absorption. An explanation on the effect of the shear flow gradients is proposed on the basis of the orientation of the rotating particles in the vortex and the size, shape, and mechanical properties of the nanoparticles.
Wandsysteme aus Fertigteilen für große Höhen
Authors: Empelmann Martin , Henke Volker , Teutsch Manfred
Published: September 2009

Bei Hallenbauten werden die Außen‐ oder Innenwände oft aus zwischen den Stützen übereinander angeordneten Wandelementen aus Stahlbeton‐Fertigteilen erstellt. Je nach den individuellen bautechnischen Anforderungen kann auf dem obersten Wandelement noch ein weiterer Wandaufbau aus leichten Porenbetonplatten erfolgen. Die Befestigung derartiger Wandelemente an den seitlich angeordneten Stützen oder anderen Bauteilen erfolgt entweder punktförmig, beispielsweise durch Dollen, oder kontinuierlich, z. B. durch Seilschlaufen. Zusätzlich können diese Wände, bei entsprechender Ausbildung auch als aussteifende Wandscheiben zur Aussteifung des Gesamtsystems oder als Brandwände genutzt werden. Bei der Detailausführung und dem Stabilitätsnachweis derartiger Wandscheiben sind einige Besonderheiten zu beachten, auf die in diesem Aufsatz eingegangen werden soll.

Wall Systems for Exceptional Heights

For industrial hall constructions, the outside and/or inside walls are very often constructed as precast panel wall systems, with single concrete wall panels mounted on top of each other. According to the design requirements the top panel can be loaded by the weight of a further wall system, very often consisting of lighter aereated concrete panels. The wall panels are normally fixed either at defined points by dowels or continuously, e.g. by a wire rope loop system. Furthermore, these wall systems, if appropriately constructed, can be used as stiffening members for the overall construction or as fire walls. For the detailing, dimensioning and stability analysis of these wall panels some special features have to be observed, which will be pointed out in this paper.