bluuebunny/crossref_metadata_2025 huggingface dataset:
Rituximab treatment in patients with primary Sjögren's syndrome: An open‐label phase II study
Authors: Pijpe J. , van Imhoff G. W. , Spijkervet F. K. L. , Roodenburg J. L. N. , Wolbink G. J. , Mansour K. , Vissink A. , Kallenberg C. G. M. , Bootsma H.
Published: September 2005

Objective

To investigate the safety and efficacy of B cell depletion treatment of patients with active primary Sjögren's syndrome of short duration (early primary SS) and patients with primary SS and mucosa‐associated lymphoid tissue (MALT)–type lymphoma (MALT/primary SS).

Methods

Fifteen patients with primary SS were included in this phase II trial. Inclusion criteria for the early primary SS group were B cell hyperactivity (IgG >15 gm/liter), presence of autoantibodies (IgM rheumatoid factor, anti‐SSA/SSB), and short disease duration (<4 years). Inclusion criteria for the MALT/primary SS group were primary SS and an associated MALT‐type lymphoma (Ann Arbor stage IE) localized in the parotid gland. Patients were treated with 4 infusions of rituximab (375 mg/m2) given weekly after pretreatment with prednisone (25 mg) and clemastine. Patients were evaluated, using immunologic, salivary/lacrimal function, and subjective parameters, at baseline and at 5 and 12 weeks after the first infusion.

Results

Significant improvement of subjective symptoms and an increase in salivary gland function was observed in patients with residual salivary gland function. Immunologic analysis showed a rapid decrease of peripheral B cells and stable levels of IgG. Human antichimeric antibodies (HACAs) developed in 4 of 15 patients (27%), all with early primary SS. Three of these patients developed a serum sickness–like disorder. Of the 7 patients with MALT/primary SS, complete remission was achieved in 3, and disease was stable in 3 and progressive in 1.

Conclusion

Findings of this phase II study suggest that rituximab is effective in the treatment of primary SS. The high incidence of HACAs and associated side effects observed in this study needs further evaluation.
Prevalence of Barrett's esophagus in systemic sclerosis
Authors: Wipff J. , Allanore Y. , Soussi F. , Terris B. , Abitbol V. , Raymond J. , Chaussade S. , Kahan A.
Published: September 2005

Objective

The esophagus is the most commonly affected gastrointestinal area in systemic sclerosis (SSc). Patients with SSc frequently develop gastroesophageal reflux, esophageal injury, and sometimes, intestinal metaplasia, or Barrett's esophagus (BE), which may increase the risk of esophageal adenocarcinoma. This study sought to determine the prevalence of BE and esophageal adenocarcinoma in a cohort of SSc patients.

Methods

One hundred ten SSc patients who were receiving long‐term treatment with proton‐pump inhibitors (PPIs) were assessed systematically by esophageal manometry and endoscopy. Esophageal biopsies were performed when macroscopic abnormalities were detected, and BE was diagnosed histologically.

Results

Among the 110 patients, 14 had BE (12.7%). None of the patients with BE had adenocarcinoma, but 3 of the 14 patients (21%) had dysplasia on esophageal biopsy. Similar proportions of patients with and without BE had abnormal peristalsis and decreased lower esophageal sphincter pressure. No association between BE and other disease characteristics was demonstrated.

Conclusion

In this study, 12.7% of SSc patients who had been treated with PPIs for long periods had BE, similar to the prevalence in patients with gastroesophageal reflux disease. Although none of the patients had esophageal adenocarcinoma, patients with BE should be followed up closely, particularly patients with dysplasic BE. Long‐term prospective studies are warranted to determine the phenotype of SSc patients at high risk of developing dysplasia or esophageal adenocarcinoma.
Fcγ receptor type IIIA polymorphisms influence treatment outcomes in patients with inflammatory arthritis treated with tumor necrosis factor α–blocking agents
Authors: Tutuncu Zuhre , Kavanaugh Arthur , Zvaifler Nathan , Corr Maripat , Deutsch Reena , Boyle David
Published: September 2005

Objective

To determine whether polymorphisms in Fcγ receptor type IIIA (FcγRIIIA) correlate with clinical efficacy in patients with rheumatoid arthritis (RA) and patients with psoriatic arthritis (PsA) being treated with tumor necrosis factor α (TNFα) inhibitors.

Methods

The study group comprised 30 patients with RA and 5 patients with PsA. Patients were classified as being very good responders (n = 23) or nonresponders (n = 12) to therapy with TNF blocking agents. Whole blood was obtained from all patients, and DNA was extracted for FcγRIIIA analysis. The FcγRIIIA‐158 polymorphism was determined using an allele‐specific polymerase chain reaction assay.

Results

The distribution of FcγRIIIA‐158 genotypes was as follows: for F homozygous (F/F), 31.5%; for V homozygous (V/V), 11.5%; and for V/F heterozygous (V/F), 57%. Among very good responders, the distribution of alleles was as follows: for F/F, 48%; for V/V, 13%; and for V/F, 39%. Among nonresponders, the distribution of alleles was as follows: for F/F, 0%; for V/V, 8%; and for V/F, 92%. The low‐affinity F/F homozygous genotype was found to be significantly associated with response to TNF inhibitor therapy (P < 0.01 by Fisher's exact test).

Conclusion

These results suggest that FcγRIIIA‐158 polymorphisms may affect the outcome of treatment with TNF blocking agents. Better understanding of the factors affecting responses to these agents could result in improved outcomes of treatment.
Tumor necrosis factor receptor I from patients with tumor necrosis factor receptor–associated periodic syndrome interacts with wild‐type tumor necrosis factor receptor I and induces ligand‐independent NF‐κB activation
Authors: Yousaf Nasim , Gould David J. , Aganna Ebun , Hammond Linda , Mirakian Rita M. , Turner Mark D. , Hitman Graham A. , McDermott Michael F. , Chernajovsky Yuti
Published: September 2005

Objective

To investigate the molecular consequences of expressing mutated forms of tumor necrosis factor receptor I (TNFRI) as found in patients with TNFR‐associated periodic syndrome (TRAPS).

Methods

We cloned and expressed full‐length wild‐type (WT) and T50K and P46L variants of TNFRI using a new tightly regulated doxycycline‐dependent expression system. This system enabled the study of molecular interactions between these receptors at both physiologic and pathophysiologic levels of expression.

Results

We used chemical crosslinking on the cell surface to show that WT and mutant forms of TNFRI, derived from TRAPS patients, interact in the absence of TNF ligand. Doxycycline‐controlled up‐regulation of one TNFRI allele, either WT or mutant, caused down‐regulation of the other allele, indicating dynamic control of cell surface assembly. We also demonstrated that increased expression of mutant TNFRI (T50K) was associated with a parallel increase in NF‐κB p65 (RelA) subunit activation, which did not occur with increased expression of WT TNFRI.

Conclusion

The T50K TRAPS‐related variant is capable of sustaining inappropriate NF‐κB activation, resulting in persistent autoinflammation in target organs such as skin, synovial membrane, and the central nervous system. We conclude that some of the inflammatory processes seen in TRAPS do not involve direct interaction of TNF with its receptors, but that other proinflammatory mechanisms capable of up‐regulating TNFRI expression may cause cellular activation through the NF‐κB signaling pathway.
Involvement of chemokines and type 1 cytokines in the pathogenesis of hepatitis C virus–associated mixed cryoglobulinemia vasculitis neuropathy
Authors: Saadoun David , Bieche Ivan , Maisonobe Thierry , Asselah Tarik , Laurendeau Ingrid , Piette Jean Charles , Vidaud Michel , Cacoub Patrice
Published: September 2005

Objective

To examine the expression profiles of a large number of genes within typical vasculitic nerve lesions in patients with mixed cryoglobulinemia (MC) vasculitis in order to better characterize the molecules involved in cellular tissue activation and trafficking.

Methods

The quantitative expression of 19 genes coding for cytokines, chemokines, and their receptors in the nerve lesions of 9 patients with hepatitis C virus (HCV)–associated MC vasculitis, 7 with idiopathic polyarteritis nodosa (PAN) (rheumatic disease controls), and 8 patients with noninflammatory idiopathic neuropathy (noninflammatory neuropathy controls) was assessed using a real‐time reverse transcriptase–polymerase chain reaction procedure.

Results

Compared with the noninflammatory controls, HCV‐MC vasculitis patients had a significantly higher expression of Th1 cytokines in vasculitic nerve lesions (mean ± SEM fold increase 33.7 ± 11.6 for interferon‐γ and 7.2 ± 1.9 for tumor necrosis factor α), whereas Th2 cytokines were absent (interleukin‐4 [IL‐4], IL‐5, and IL‐13) or were not significantly different (IL‐10). Chemokines involved in T cell and monocyte trafficking were also significantly up‐regulated in the HCV‐MC vasculitis patients (mean ± SEM fold increase 27.4 ± 8.3 for macrophage inflammatory protein 1α [MIP‐1α], 19.9 ± 5.7 for MIP‐1β, and 7.2 ± 1.5 for CXCR3). Compared with patients with idiopathic PAN, there was a trend toward higher expression of MIP‐1α and CXCR3 in HCV‐MC vasculitis patients (mean ± SEM fold increase 27.4 ± 8.3 versus 5.3 ± 3.4 for MIP‐1α and 7.2 ± 1.5 versus 2.5 ± 0.9 for CXCR3).

Conclusion

This study is the first to demonstrate a role of cellular immunity and Th1 lymphocytes in the pathogenesis of HCV‐MC vasculitic nerve lesions.
Cerebral and corpus callosum atrophy in systemic lupus erythematosus
Authors: Appenzeller Simone , Rondina Jane Maryam , Li Li Min , Costallat Lilian T. L. , Cendes Fernando
Published: September 2005

Objective

To determine cerebral and corpus callosum volumes in patients with systemic lupus erythematosus (SLE), using semiautomatic magnetic resonance imaging (MRI) volumetric measurements, and to determine possible relationships between a reduction in cerebral volume and disease duration, total corticosteroid dose, neuropsychiatric manifestations, and the presence of antiphospholipid antibodies.

Methods

We studied 115 consecutive patients with SLE and 44 healthy volunteers. A complete clinical, laboratory, and neurologic evaluation was performed. MRI scans were obtained through a standardized protocol. Sagittal T1‐weighted images were used for semiautomatic volumetric measurements. We compared SLE patients with controls using the 2‐sample t‐test. Analysis of variance was used to test for differences between groups, followed by Tukey's post hoc test for pairwise comparisons, when necessary. Linear regression was used to analyze the association between cerebral atrophy and disease duration and total corticosteroid dose.

Results

Cerebral and corpus callosum volumes were significantly smaller in patients with SLE compared with healthy volunteers (P < 0.001). Reduced cerebral and corpus callosum volumes were related to disease duration (P < 0.001). Patients with a history of central nervous system (CNS) involvement more frequently had a reduction in cerebral and corpus callosum volumes (P < 0.001). Patients with cognitive impairment had significantly reduced corpus callosum and cerebral volumes when compared with SLE patients without cognitive impairment (P = 0.001). Cerebral and corpus callosum volumes were not associated with the total corticosteroid dose or the presence of antiphospholipid antibodies.

Conclusion

In patients with SLE, a reduction in cerebral and corpus callosum volumes is associated with disease duration, a history of CNS involvement, and cognitive impairment. The total corticosteroid dose and the presence of antiphospholipid antibodies were not associated with more pronounced atrophy.
An independent role of protective HLA class II alleles in rheumatoid arthritis severity and susceptibility
Authors: van der Helm‐van Mil Annette H. M. , Huizinga Tom W. J. , Schreuder Geziena M. Th. , Breedveld Ferdinand C. , de Vries René R. P. , Toes René E. M.
Published: September 2005

Objective

To prospectively investigate the effect of the DERAA‐encoding HLA alleles on disease susceptibility and severity in a large cohort of patients with rheumatoid arthritis (RA), and to differentiate protective effects from nonpredisposition by comparing subgroups of patients with an equal amount of predisposition alleles.

Methods

HLA class II alleles were determined in 440 patients with early RA and in 423 healthy controls. In order to study the effect of HLA on disease severity, radiographic joint destruction was evaluated, using the modified Sharp/van der Heijde method, during 4 years of followup.

Results

The presence of DERAA‐encoding HLA–DRB1 alleles conferred a lower risk of developing RA for both the presence and absence of SE alleles (odds ratio 0.6). At all time points, radiographic destruction was significantly less severe in DERAA‐positive patients with 1 SE allele compared with DERAA‐negative patients with 1 SE allele. Additionally, a protective effect of DERAA was detected in the groups of patients who were prone to having more severe disease because of the presence of anti–cyclic citrullinated peptide antibodies or because of smoking.

Conclusion

DERAA‐encoding HLA–DRB1 alleles independently protect against RA and are associated with less severe disease.
RNA released from necrotic synovial fluid cells activates rheumatoid arthritis synovial fibroblasts via toll‐like receptor 3
Authors: Brentano Fabia , Schorr Olivier , Gay Renate E. , Gay Steffen , Kyburz Diego
Published: September 2005

Objective

To assess the expression of Toll‐like receptor 3 (TLR‐3) protein in synovial tissues and cultured synovial fibroblasts obtained from patients with rheumatoid arthritis (RA) and osteoarthritis (OA) and to investigate the consequences of stimulation of cultured synovial fibroblasts with TLR‐3 ligands.

Methods

TLR‐3 expression in synovial tissues was determined by immunohistochemistry and immunofluorescence, and expression in cultured RA synovial fibroblasts (RASFs) was determined by fluorescence‐activated cell sorting and real‐time polymerase chain reaction techniques. TLR‐3 signaling was assessed by incubating RASFs with poly(I‐C), lipopolysaccharide, palmitoyl‐3‐cysteine‐serine‐lysine‐4, or necrotic synovial fluid cells from RA patients in the presence or absence of hydroxychloroquine or Benzonase. Subsequent determination of interferon‐β (IFNβ), CXCL10, CCL5, and interleukin‐6 (IL‐6) protein production in the culture supernatants was performed by enzyme‐linked immunosorbent assays.

Results

TLR‐3 protein expression was found to be higher in RA synovial tissues than in OA synovial tissues. TLR‐3 expression was localized predominantly in the synovial lining, with a majority of the TLR‐3–expressing cells coexpressing fibroblast markers. Stimulation of cultured RASFs with the TLR‐3 ligand poly(I‐C) resulted in the production of high levels of IFNβ, CXCL10, CCL5, and IL‐6 protein. Similarly, coincubation of RASFs with necrotic synovial fluid cells from patients with RA resulted in up‐regulation of these cytokines and chemokines in a TLR‐3–dependent manner.

Conclusion

Our findings demonstrate the expression of TLR‐3 in RA synovial tissue and the activation of RASFs in vitro by the TLR‐3 ligand poly(I‐C) as well as by necrotic RA synovial fluid cells, and indicate that RNA released from necrotic cells might act as an endogenous TLR‐3 ligand for the stimulation of proinflammatory gene expression in RASFs.
Selective expansion of a monocyte subset expressing the CD11c dendritic cell marker in the Yaa model of systemic lupus erythematosus
Authors: Amano Hirofumi , Amano Eri , Santiago‐Raber Marie‐Laure , Moll Thomas , Martinez‐Soria Eduardo , Fossati‐Jimack Liliane , Iwamoto Masahiro , Rozzo Stephen J. , Kotzin Brian L. , Izui Shozo
Published: September 2005

Objective

Monocytosis is a unique cellular abnormality associated with the Yaa (Y‐linked autoimmune acceleration) mutation. The present study was designed to define the cellular mechanism responsible for the development of monocytosis and to characterize the effect of the Yaa mutation on the development of monocyte subsets.

Methods

We produced bone marrow chimeras reconstituted with a mixture of Yaa and non‐Yaa bone marrow cells bearing distinct Ly‐17 alloantigens, and determined whether monocytes of Yaa origin became dominant. Moreover, we defined the 2 major inflammatory (Gr‐1+,CD62 ligand [CD62L]+) and resident (Gr‐1−,CD62L−) subsets of blood monocytes in aged BXSB Yaa male mice, as compared with BXSB male mice lacking the Yaa mutation.

Results

Analysis of the Ly17 allotype of blood monocytes in chimeric mice revealed that monocytes of both Yaa and non‐Yaa origin were similarly involved in monocytosis. Significantly, the development of monocytosis paralleled a selective expansion of the resident monocyte subset compared with the inflammatory subset, and the former expressed CD11c, a marker of dendritic cells. Neither monocytosis nor the change in monocyte subpopulations, including CD11c expression, was observed in Yaa‐bearing C57BL/6 mice, in which systemic lupus erythematosus (SLE) fails to develop.

Conclusion

Our results suggest that Yaa‐associated monocytosis is not attributable to an intrinsic abnormality in the growth potential of monocyte lineage cells bearing the Yaa mutation and that the Yaa mutation could lead to the expansion of dendritic cells, thereby contributing to the accelerated development of SLE.
Preclinical pharmacokinetics of a novel HIV‐1 attachment inhibitor BMS‐378806 and prediction of its human pharmacokinetics
Authors: Yang Zheng , Zadjura Lisa , D'Arienzo Celia , Marino Anthony , Santone Kenneth , Klunk Lewis , Greene Douglas , Lin Pin‐Fang , Colonno Richard , Wang Tao , Meanwell Nicholas , Hansel Steven
Published: September 2005

BMS‐378806 is a prototype of novel HIV attachment inhibitors that block the gp120 and CD4 interaction, the first step of HIV‐1 entry into cells. The present work investigated the pharmacokinetics of BMS‐378806 in rats, dogs and monkeys and assessed its in vitro permeability and metabolism. BMS‐378806 exhibited species‐dependent oral bioavailability which was 19%–24% in rats and monkeys and 77% in dogs. In rats and monkeys, absorption was prolonged, with an apparent terminal half‐life of 2.1 and 6.5 h, respectively. In rats, linear pharmacokinetics was observed between i.v. doses of 1 and 5 mg/kg and between p.o. doses of 5 and 25 mg/kg. The total body clearance was intermediate in rats and low in dogs and monkeys. The steady‐state volume of distribution was moderate (0.4–0.6 l/kg), contributing to a short half‐life (0.3–1.2 h) after i.v. dosing. Studies in bile‐duct cannulated rats together with intraportal infusion studies revealed that the renal and hepatic clearance each accounted for 30% and 70% of the total elimination in rats, with the hepatic clearance largely being oxidative metabolism. In vitro, BMS‐378806 was not highly protein bound (44%–73%). The Caco‐2 permeability was modest (51 nm/s) and confounded by P‐glycoprotein mediated efflux transport. Both of these may contribute to the low brain penetration observed in rats (brain/plasma AUC ratio=0.06). In human liver microsomes BMS‐378806 was equally metabolized by cytochrome P450 1A2, 2D6 and 3A4 and did not inhibit major drug‐metabolizing enzymes to a significant extent. Based on in vitro and animal data, a mechanistic approach that factors in absorption and first‐pass metabolism was employed to predict the human oral bioavailability of BMS‐378806 (ca 20%). This, together with the complex Dedrick plot method, was used to simulate human oral profiles and to project an efficacious dose. These study results offer a comprehensive assessment of the developability of BMS‐378806 and provide important guidance to improving absorption and half‐life of future compounds in the series. The current studies also demonstrate the value and approaches of understanding pharmacokinetic properties in the early stage of drug discovery. Copyright © 2005 John Wiley & Sons, Ltd.
Production of a recombinant cholera toxin B subunit‐insulin B chain peptide hybrid protein by Brevibacillus choshinensis expression system as a nasal vaccine against autoimmune diabetes
Authors: Yuki Yoshikazu , Hara‐Yakoyama Chisato , Guadiz Abigail A.E. , Udaka Shigezo , Kiyono Hiroshi , Chatterjee Subhendra
Published: September 2005

Mucosally induced tolerance is an attractive strategy for preventing or reducing autoimmune diseases. Here, we produced a recombinant CTB fusion protein linked with autoantigen T cell epitope of insulin B chain peptide 9–23 (C19S) at levels up to 200 mg/L culture media in Brevibacillus choshinensis secretion‐expression system. Receptor‐competitive assay showed that the CTB‐insulin peptide binds to GM1 receptor almost equivalent degree as the native form of CTB. Non‐obese diabetes (NOD) mice that spontaneously develop an insulin‐dependent diabetes were nasally immunized with CTB‐insulin peptide (5 µg) for three times. The nasal treatment significantly reduced the development of insulin‐dependent diabetes and peptide specific DTH responses after systemic immunization with the insulin peptide B 9–23(C19S) in CFA. Nasal administration of as high as 50 µg of the peptide alone demonstrated a similar level of the disease inhibition. In contrast, all mice given 5 µg of the insulin peptide alone or 5 µg of insulin peptide with 25 µg of the free form of CTB did not lead to the suppression of diabetes development and DTH responses. Because molecular weight of the insulin peptide is about one tenth of that of the CTB‐insulin peptide, the results demonstrate that the recombinant hybrid of autoantigen and CTB increased its tolerogenic potential for nasal administration by up 100‐fold on molar base of autoantigen peptide. Taken together, nasally‐induced tolerance by administration of the recombinant B.choshinensis‐derived hybrid protein of CTB and autoantigen T cell‐epitope peptide could be useful mucosal immunetherapy for the control of T cell‐mediated autoimmune diseases. © 2005 Wiley Periodicals, Inc.
Structure of a cellulose degrading bacterial community during anaerobic digestion
Authors: O'Sullivan Cathryn A. , Burrell Paul C. , Clarke William P. , Blackall Linda L.
Published: September 2005

It is widely accepted that cellulose is the rate‐limiting substrate in the anaerobic digestion of organic solid wastes and that cellulose solubilisation is largely mediated by surface attached bacteria. However, little is known about the identity or the ecophysiology of cellulolytic microorganisms from landfills and anaerobic digesters. The aim of this study was to investigate an enriched cellulolytic microbial community from an anaerobic batch reactor. Chemical oxygen demand balancing was used to calculate the cellulose solubilisation rate and the degree of cellulose solubilisation. Fluorescence in situ hybridisation (FISH) was used to assess the relative abundance and physical location of three groups of bacteria belonging to the Clostridium lineage of the Firmicutes that have been implicated as the dominant cellulose degraders in this system. Quantitation of the relative abundance using FISH showed that there were changes in the microbial community structure throughout the digestion. However, comparison of these results to the process data reveals that these changes had no impact on the cellulose solubilisation in the reactor. The rate of cellulose solubilisation was approximately stable for much of the digestion despite changes in the cellulolytic population. The solubilisation rate appears to be most strongly affected by the rate of surface area colonisation and the biofilm architecture with the accepted model of first order kinetics due to surface area limitation applying only when the cellulose particles are fully covered with a thin layer of cells. © 2005 Wiley Periodicals, Inc.
Role of cranberry juice on molecular‐scale surface characteristics and adhesion behavior of Escherichia coli
Authors: Liu Yatao , Black Matthew A. , Caron Lizabeth , Camesano Terri A.
Published: September 2005

Cranberry juice has long been believed to benefit the prevention and treatment of urinary tract infections (UTIs). As the first step in the development of infection, bacterial adhesion is of great research interest, yet few studies have addressed molecular level adhesion in this context. P‐fimbriated Escherichia coli play a major role in the development of a serious type of UTI, acute pyelonephritis. Experiments were conducted to investigate the molecular‐scale effects of cranberry juice on two E. coli strains: HB101, which has no fimbriae, and the mutant HB101pDC1 which expresses P‐fimbriae. Atomic force microscopy (AFM) was used to investigate both bacterial surface characteristics and adhesion forces between a probe surface (silicon nitride) and the bacteria, providing a direct evaluation of bacterial adhesion and interaction forces. Cranberry juice affected bacterial surface polymer and adhesion behavior after a short exposure period (<3 h). Cranberry juice affected the P‐fimbriated bacteria by decreasing the adhesion forces between the bacterium and tip and by altering the conformation of the surface macromolecules on E. coli HB101pDC1. The equilibrium length of polymer (P‐fimbriae) on this bacterium decreased from ∼148 to ∼48 nm upon being exposed to cranberry juice. Highly acidic conditions were not necessary for the prevention of bacterial adhesion, since neutralization of cranberry juice solutions to pH = 7.0 allowed us to observe differences in adhesion between the E. coli strains. Our results demonstrate molecular‐level changes in the surfaces of P‐fimbriated E. coli upon exposure to neutralized cranberry juice. © 2005 Wiley Periodicals, Inc.
Protective effects of long term dietary restriction on swimming exercise‐induced oxidative stress in the liver, heart and kidney of rat
Authors: Aydin Cenk , Ince Erdal , Koparan Senay , Cangul I. Taci , Naziroglu Mustafa , Ak Fusun
Published: September 2005

In this study, we evaluated the hypothesis that long term dietary restriction would have beneficial effects on the oxidative stress and antioxidant enzyme systems in liver, heart and kidney in adult male rats undergoing different intensities of swimming exercise. Sixty male, Sprague–Dawley rats were assigned as either dietary restricted on every other week day (DR) or fed ad libitum (AL) groups, and each group was further subdivided into sedentary, endurance swimming exercise training (submaximal exercise) and exhaustive swimming exercise (maximal exercise) groups. Animals in the submaximal exercise group swam 5 days/week for 8 weeks, while maximal exercise was performed as an acute bout of exercise.

In parallel with the increase in the intensity of the exercise, the degree of lipid peroxidation and protein oxidation were increased in both the DR and AL groups; however the rate of increase was lower in the DR group. Reduced glutathione (GSH), glutathione peroxidase (GSH‐Px) and glutathione reductase (GR) enzyme activities were lower in the DR group than in the AL group. In parallel with the increase in exercise intensity, GSH and GR enzyme activities decreased, whereas an increase was observed in GSH‐Px enzyme activity.

In conclusion, the comparison between the DR and AL groups with the three swimming exercise conditions shows that the DR group is greatly protected against different swimming exercise‐induced oxidative stress compared with the AL group. Copyright © 2005 John Wiley & Sons, Ltd.
Transcatheter atrial septal defect closure: Modified balloon sizing technique to avoid overstretching the defect and oversizing the Amplatzer septal occluder
Authors: Carlson Karina M. , Justino Henri , O'Brien Richard E. , Dimas V. Vivian , Leonard Glenn T. , Pignatelli Ricardo H. , Mullins Charles E. , Smith E. O'Brian , Grifka Ronald G.
Published: September 2005

The objective of this study was to evaluate a new technique of sizing atrial septal defects (ASDs) for transcatheter device closure. ASD closure using the Amplatzer septal occluder (ASO) device is commonly performed. Complications, including arrhythmias, pericardial effusions, and perforations, may be related to oversizing ASDs and choosing larger devices. Two methods were used to size ASDs using a compliant balloon. In some patients, the balloon was inflated until a waist was visible [(+)waist]; in others, only until no shunting was demonstrable by echocardiogram [echo; (−)waist]. The device was selected and implanted using standard procedure and echo guidance. One hundred seventeen patients underwent secundum ASD closure with an ASO device. There were 43 patients in the (−)waist group and 74 in the (+)waist group. All devices were implanted successfully. The initial echo ASD diameter was larger in the (−)waist group compared to the (+)waist group (P = 0.01). There was a smaller difference between the initial echo and balloon‐sized ASD diameters in the (−)waist group (P < 0.02). ASO device size implanted (in mm greater than echo ASD diameter) was smaller in the (−)waist group (P < 0.01). There were 0/43 complications in the (−)waist group and 5/74 in the (+)waist group. The complete closure rate was the same in both groups. Sizing an ASD by inflating a compliant balloon just until shunting is eliminated, and not until a waist is visible, results in less overstretching of the ASD and selection of a smaller ASO device, achieving similar closure rates and potentially fewer complications. Catheter Cardiovasc Interv 2005;. © 2005 Wiley‐Liss, Inc.
Non‐negativity constraints for elimination of multiple solutions in fitting of multivariate kinetic models to spectroscopic data
Authors: Jaumot Joaquim , Gemperline Paul J. , Stang Alexandra
Published: September 2005

Multiple solutions arise when fitting complicated multi‐step kinetic models to spectroscopic data. For consecutive reactions of the type A→B→C this well‐known ambiguity is due to the presence of multiple equivalent global minima in the response surfaces associated with the non‐linear least squares fitting of rate constants to spectroscopic data. Several methods have been described to overcome the ambiguity when fitting consecutive reactions with univariate data but few attempts to solve the problem have been described for multivariate data. Additionally, for complicated multi‐step reaction schemes there may be several local minima that make selection of the initial parameter guesses difficult. This paper reports a general approach to overcome these types of ambiguities in multivariate kinetic fitting methods using non‐negativity constraints for the determination of the pure component spectra estimated during the model‐fitting process. Under many conditions these constraints reduce or eliminate entirely the incorrect local minima. The effectiveness and reliability of the new constraints were tested with several simulated and real data sets. Copyright © 2005 John Wiley & Sons, Ltd.
Novel Multichiral Diols and Diamines by Highly Stereoselective Pinacol Coupling of Planar Chiral [2.2]Paracyclophane Derivatives
Authors: Sergeeva Elena V. , Rozenberg Valeria I. , Antonov Dmitrii Yu. , Vorontsov Evgenii V. , Starikova Zoya A. , Fedyanin Ivan V. , Hopf Henning
Published: September 2005

The TiCl4/Zn‐mediated intermolecular pinacol coupling of the planar chiral carbonyl compounds [2.2]paracyclophane‐4‐carbaldehyde, 4‐acetyl[2.2]paracyclophane (ketone) and the four regioisomeric 5‐, 7‐, 12‐ and 13‐methoxy[2.2]paracyclophane‐4‐carbaldehydes as well as the pTosOH–Zn/Cu‐promoted coupling of their N‐substituted imines is described. Coupling of the enantiomerically pure substrates (most of carbonyl compounds and all imines) occurs stereoselectively giving rise to diastereomerically pure 1,2‐diols and 1,2‐diamines. Racemic aldehydes and ketone react with different degrees of stereoselectivity (depending on the substituents in certain positions) and produce one to three diastereomers. 7‐Methoxy[2.2]paracyclophane‐4‐carbaldehyde undergoes a tandem pinacol coupling–pinacol rearrangement to yield bis‐(7‐methoxy[2.2]paracyclophane‐4‐yl)acetaldehyde. Coupling of the racemic imines produces a mixture of single racemic D,L‐diamine and single meso‐diamine in each case. The stereoselective formation of the asymmetric centres is governed by the planar chiral [2.2]paracyclophanyl moiety. The techniques elaborated are extended to the intramolecular coupling of [2.2]paracyclophane‐4,13‐dicarbaldehyde and its bis‐N‐phenylimine, resulting in stereoselective formation of the chiral triply‐bridged diol and exclusive formation of the meso‐diamine. X‐Ray investigations of several diols and diamines have been carried out and the structural features of these derivatives are discussed.
Silylenes, Silenes, and Disilenes: Novel Silicon‐Based Reagents for Organic Synthesis?
Authors: Ottosson Henrik , Steel Patrick G.
Published: September 2005

Silylenes, silenes, and disilenes are silicon analogues of carbenes and alkenes. Since the first detection and isolation of these species a few decades ago, focus has been given to their fundamental structure and reactivity properties. Recent developments show that the time is set to exploit their unique chemistry in applied areas. Emerging applications in catalysis and stereoselective synthesis point to a new field within synthetic organosilicon chemistry.
Charge and Spin Correlations of a One‐Dimensional Electron Gas on the Continuum
Authors: Casula Michele , Senatore Gaetano
Published: September 2005

We present a variational Monte Carlo study of a model one‐dimensional electron gas on the continuum, with long‐range interaction (1/r decay). At low density, the reduced dimensionality brings about pseudonodes of the many‐body wavefunction, yielding nonergodic behavior of naive Monte Carlo sampling, which affects the evaluation of pair correlations and the related structure factors. The problem is, however, easily solved, and we carefully analyzed the structure factors obtained from an optimal trial function, finding good agreement with the exact predictions for a Luttinger‐like Hamiltonian with an interaction similar to the one used in the present study.
Efficient Evaluation of Nonlocal Pseudopotentials via Euler Exponential Spline Interpolation
Authors: Lee Hee‐Seung , Tuckerman Mark E. , Martyna Glenn J.
Published: September 2005

An Euler exponential spline (EES) based formalism is employed to derive new expressions for the electron–atom nonlocal pseudopotential interaction (NL) in electronic structure calculations performed using a plane wave basis set that can be computed more rapidly than standard techniques. Two methods, one that is evaluated by switching between real and reciprocal space via fast Fourier transforms, and another that is evaluated completely in real space, are described. The reciprocal‐space or g‐space‐based technique, NLEES‐G, scales as NMlogM∼N2logN, where N is the number of electronic orbitals and M is the number of plane waves. The real‐space based technique, NLEES‐R, scales as N2. The latter can potentially be used within a maximally spatially localized orbital method to yield linear scaling, while the former could be employed within a maximally delocalized orbital method to yield NlogN scaling. This behavior is to be contrasted with standard techniques, which scale as N3. The two new approaches are validated using several examples, including solid silicon and liquid water, and demonstrated to be improvements on other, reduced‐order nonlocal techniques. Indeed, the new methods have a low overhead and become more efficient than the standard technique for systems with roughly 20 or more atoms. Both NLEES methods are shown to work stably and efficiently within the Car–Parrinello ab initio molecular dynamics framework, owing to the existence of p−2 continuous derivatives of a pth‐order spline.
Space‐time ring‐TCM codes with CPM based on the decomposed model for transmission over Rayleigh fading channels
Authors: Pereira A. , Carrasco R. A.
Published: September 2005

Space–time (ST) coding is a proved technique for achieving high data rates in 3G mobile systems that combines coding, modulation and multiple transmitters and receivers. A novel algorithm is proposed for ST ring trellis‐coded modulation (ST‐RTCM) systems with continuous‐phase modulation (CPM) when the channel coefficients are known to the receiver. This algorithm is based on the CPM decomposed model, which exploits the memory properties of this modulation method, resulting in a straightforward implementation of joint ST coding and CPM, which is particularly suitable for ring codes. This new scheme is used to investigate the performance of the delay diversity code with CPM over slow Rayleigh fading channels, in particular with MSK which is one of the most widely used modulation methods of continuous phase. Furthermore, a feedback version of delay diversity allowed by the decomposition is tested in 1REC and 1RC systems. This feedback configuration is seen to provide good results for low signal‐to‐noise ratios. Simulations results are also provided for multilevel ST‐RTCM codes that achieve a higher throughput than MSK‐coded systems. Additionally the serial concatenation of an outer Reed–Solomon code with an ST‐RTCM code is shown, this combination further reduces the error probability and achieves even more reliable communications. Copyright © 2005 John Wiley & Sons, Ltd.
Diffuse soft tissue emphysema in anorexia nervosa: A case report
Authors: Lin Liang‐Yu , Kwok Ching‐Fai , Tang Kam‐Tsun , Ho Low‐Tone , Lin Hong‐Da
Published: September 2005

Objective

Anorexia nervosa (AN) is an eating disorder that occurs mainly among young females and its prevalence has increased in recent decades.

Methods

We reported a patient with AN with spontaneous diffuse soft tissue emphysema and bicytopenia, both of which are very rare complications of AN. Our patient, a 20‐year‐old woman, had lost 41.6% of her previous body weight within 9 months. Her body mass index was 10.8 and amenorrhea had persisted for 5 months.

Results

After admission, she was diagnosed with AN‐restrictive subtype. She was noted to have crunching sounds in the neck and upper chest wall during hospitalization. A chest X‐ray and chest computed tomography scan both revealed diffuse soft tissue emphysema including subcutaneous emphysema, pneumomediastinum, and pneumoretroperitoneum.

Discussion

Diffuse soft tissue emphysema improved gradually and completely resolved on the 21st day of hospitalization. This condition seems to be benign and only a short period of hospitalization is required. © 2005 by Wiley Periodicals, Inc.
Antigen delivery via two molecules on the CD8– dendritic cell subset induces humoral immunity in the absence of conventional “danger”
Authors: Corbett Alexandra J. , Caminschi Irina , McKenzie Brent S. , Brady Jamie L. , Wright Mark D. , Mottram Patricia L. , Hogarth P. Mark , Hodder Anthony N. , Zhan Yifan , Tarlinton David M. , Shortman Ken , Lew Andrew M.
Published: September 2005

Targeting antigen to dendritic cells (DC) in vivo might be an effective method of modulating immune responses. Given the functional specializations among DC subsets, we investigated how targeting different receptors on different DC subsets may influence antibody (Ab) production. We show here that targeting FIRE (F4/80‐like receptor) or CIRE (C‐type lectin receptor), two molecules expressed on the surface of immature CD8– DC in the mouse, increases Ab production 100–1000‐fold over a non‐targeted control. This response was equivalent to that achieved with CpG adjuvant. In contrast, targeting CD205, which is primarily expressed on CD8+ DC, did not elicit an Ab response unless an adjuvant was added. Strong Ab responses in FcRγ–/– mice, and with the use of F(ab')2 fragments, confirmed that FIRE and CIRE targeting was due to specific rather than FcR or complement binding. Our findings may reflect differences in the ability of CD8+ and CD8– DC subsets to stimulate immune responses in vivo. Although the consensus view is that Ag presentation on DC in their steady state leads to tolerance, the Ab enhancement from FIRE and CIRE targeting in the apparent absence of any “danger” or inflammatory signal would suggest that targeting certain DC molecules can supplant the need for external adjuvants for eliciting immune responses.
The TRAF6, but not the TRAF2/3, binding domain of CD40 is required for cytokine production in human lung fibroblasts
Authors: Purkerson Jeffrey M. , Smith Roger S. , Pollock Stephen J. , Phipps Richard P.
Published: September 2005

Fibroblasts are key effector cells in inciting inflammation, wound healing, and scarring. CD40, a member of the TNF receptor superfamily, mediates intercellular communication between fibroblasts and cells that express CD154 (CD40L), including T lymphocytes and platelets. To better understand the mechanisms by which CD40 regulates fibroblast function in inflammation and scarring, we examined the ability of CD40 cytoplasmic tail regions (CD40ct) containing the TRAF6 or the TRAF2/3 binding domains to regulate cytokine and chemokine expression by primary human lung fibroblasts. The full‐length human CD40ct, the first 35 amino acids of the CD40ct encompassing the TRAF6 binding site (1–35), and amino acids 35–53 containing the TRAF2/TRAF3 binding domain were expressed in human lung fibroblasts as fusion proteins with the extracellular domain of human CD8α by retroviral transduction. The TRAF6, but not the TRAF2/3, binding domain was found to regulate IL‐8 and IL‐6 production, and induce activation of NF‐κB and Jun kinase in lung fibroblasts, demonstrating for the first time that CD40ct domains can function independently to regulate pro‐inflammatory responses of primary human fibroblasts. Thus, targeting TRAF6 function through pharmacological intervention may represent a viable strategy for modulating localized inflammation.
Solvothermal Synthesis of Metastable γ‐MnS Hollow Spheres and Control of Their Phase
Authors: Lei Shuijin , Tang Kaibin , Yang Qing , Zheng Huagui
Published: September 2005

A solvothermal route has been developed to prepare metastable wurtzite‐structure γ‐MnS hollow spheres from anhydrous manganese chloride, sulfur powder, and potassium borohydride in ethylene glycol at 150–180 °C. The metastable γ‐MnS and stable α‐MnS were characterized by X‐ray diffraction, X‐ray photoelectron spectroscopy, field‐emission scanning electronic microscopy, scanning electron microscopy, transmission electron microscopy, and photoluminescence. Experiments show that the reaction temperature, the solvent, and the concentration and reducibility of the reductant are the crucial factors affecting the phase of the product. A possible growth mechanism for the hollow sphere is proposed. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)
Effect of metals on herbicides–α‐synuclein association: A possible factor in neurodegenerative disease studied by capillary electrophoresis
Authors: André Claire , Truong Tong T. , Robert Jean Francois , Guillaume Yves C.
Published: September 2005

The aggregation of α‐synuclein in the dopaminergic neurons of the substantia nigra is a critical step in the Parkinson's disease (PD). The etiology of the disease is unknown but recent epidemiological and experimental studies have renewed interest in the hypothesis that environmental factors, especially herbicides and metals, have a role on the pathogenesis of PD. For the first time, the association constants of α‐synuclein with five herbicides have been calculated using a capillary electrophoresis (CE) method. In addition, the effect of a number of metals on this binding has been investigated. It appears that the herbicides preferentially bind to a partially folded intermediate conformation of α‐synuclein induced by manganese, aluminium, cadmium, copper and zinc. Then, metal increases the synuclein–herbicide association. However, this study shows contrasting actions with the antibiotic rifampicin and magnesium addition leading to a decrease of the α‐synuclein–herbicide interaction even if other metals are present in the bulk solvent. Considering epidemiological studies, all these results suggest an underlying molecular basis for PD and related body diseases.
Separation of living and dead polymers in synthetic polypeptide mixtures by nonaqueous capillary electrophoresis using differences in ionization states
Authors: Souaïd Eddy , Cottet Hervé
Published: September 2005

The complexity in the mechanisms of polymerization of N‐carboxyanhydrides requires the development of new analytical techniques able to separate mixtures of synthetic polypeptides. This work focuses on the separation of poly(Nϵ‐trifluoroacetyl‐L‐lysine) (PTLL) mixtures by nonaqueous capillary electrophoresis (CE). The main goal of this work was to find electrophoretic conditions that permit the separation and the quantification of the dead polymer families that were previously identified in the samples. The influence of the pH of the electrolyte on the selectivity of the separation was carefully investigated. The mechanisms of separation of the PTTLs are discussed as a function of their ionization state. The separations obtained on a noncovalently coated capillary were compared with those obtained on a fused‐silica capillary. Finally, using two different electrolytes, it is possible to quantify the three families of PTLLs, namely, the living PTLLs, the dead PTLLs with N‐formyl end group and the dead PTLLs with a carboxylic end group. These results confirm the importance of CE for the separation of synthetic organic polymers in nonaqueous electrolytes.
Effects of the limited analyte solubility on its mobility and zone shape: Electrophoretic behavior of sanguinarine and chelerythrine around pH 7
Authors: Vespalec Radim , Vlčková Markéta , Kubáň Vlastimil
Published: September 2005

Electrophoretic mobilities and shapes of zones of sanguinarine and chelerythrine in aqueous media around pH 7 are affected by limited solubility of their uncharged forms and by the pH‐dependent chemical equilibrium between cationic and uncharged forms of these alkaloids. The sanguinarine solubility in sodium MOPS of pH 7.4 was estimated at 50 µmol·L−1. Sanguinarine zones in this buffer have the shape of tailed peak with concentration‐independent mobility if the injected sanguinarine concentration exceeds this solubility limit only slightly. The chelerythrine solubility is higher because of lower dissociation constants of its cations. Precipitation of sanguinarine and chelerythrine with the phosphate anions decelerates their electrophoretic transport in phosphate buffer. Sanguinarine solubility is 5 µmol·L−1 at the most in 13 mmol·L−1 sodium phosphate buffer of pH 7.4. Acidifying of the sample up to pH 3 decreases the tailing of the peaks of sanguinarine and chelerythrine and contributes to the rise of sharp maxima of their migrating zones. Any capillary coating deteriorates the peak shape.