bluuebunny/crossref_metadata_2025_split huggingface dataset:
A novel VEGFR3 mutation causes Milroy disease
Authors: Butler Matthew G. , Dagenais Susan L. , Rockson Stanley G. , Glover Thomas W. 
Published: April 2007

AbstractMilroy disease, also known as primary congenital lymphedema, is a hereditary form of lymphedema with autosomal dominant inheritance. Individuals with Milroy disease are typically characterized by congenital onset of lymphedema of the lower limbs due to hypoplasia of the lymphatic vessels. The genetic basis of most cases of Milroy disease has not been established, although mutations in the vascular endothelial growth factor receptor VEGFR3 (FLT‐4) are responsible for some cases with 17 mutations described to date. In this report, we describe a novel VEGFR3 mutation in exon 22 in a four‐generation family in which congenital lymphedema segregates in an autosomal dominant manner. In addition to lymphedema, affected family members had other clinical manifestations associated with Milroy disease including hydrocele, ski jump toenails, large caliber veins, and subcutaneous thickening. We screened VEGFR3 for mutations which revealed a novel 3059A > T transversion in exon 22 resulting in Q1020L missense mutation in the second tyrosine kinase domain of VEGFR3. This mutant allele segregated with lymphedema among affected individuals with incomplete penetrance. This is the first report of an exon 22 mutation in Milroy disease. © 2007 Wiley‐Liss, Inc.
Parameters affecting the grafting reaction and side reactions involved in the free‐radical melt grafting of maleic anhydride onto high‐density polyethylene
Authors: Sheshkali H. R. Z. , Assempour H. , Nazockdast H. 
Published: April 2007

AbstractThe parameters affecting the grafting reaction and side reactions in free‐radical melt grafting of maleic anhydride (MA) onto high‐density polyethylene with the aid of 2,5‐dimethyl‐2,5‐di(t‐butyl peroxy)hexane peroxide(DTBPH) have been studied using an internal mixer. MA grafting degree of the maleated samples was measured with titrometry and FTIR spectroscopy methods. The extent of chain‐branching/crosslinking side reactions was evaluated with gel content and MFI determination. The flow behavior and melt viscoelastic properties of the samples were measured using a rheometric mechanical spectrometer. DTBPH and MA concentrations, reaction temperature, rotor speed, the type and concentration of coagents were among the studied parameters. The results show that MA and DTBPH concentration has a major role on the grafting reaction, chain‐branching/crosslinking side reactions and also the grafts microstructure in the final product. The reaction temperature has a complex effect on the maleation reaction. Increasing the rotor speed causes an increase in MA grafting degree of the samples and reduces the competitive side reactions. By using Gaylord additives, gel formation reduces at the expense of a dramatic decrease in the grafting degree. MA grafting degree is increased by the use of comonomers in the reaction and this is accompanied with a decrease in crosslinking side reaction when the vinyl type styrene comonomer is used. The results of processing torque in combination with the measurements of the melt viscoelastic property and gel content of the samples provide a great insight into understanding the gel formation mechanism. © 2007 Wiley Periodicals, Inc. J Appl Polym Sci, 2007
Analysis of the effect of the amount and type of montmorillonite on the supermolecular structure, porosity, and properties of polyimidoamide fibres
Authors: Mikołajczyk Teresa , Rabiej Stanisław , Olejnik Magdalena 
Published: April 2007

AbstractThe effect of the amount and type of montmorillonite (MMT) on the supermolecular structure, porosity, and properties of polyimidoamide (PIA) fibres has been investigated. An increase in the quantity of nanoadditive incorporated into the fiber‐forming polymer from 1 to 5% results in a decrease in the strength properties of fibers. The level of the sorption parameters of PIA nanocomposite fibers depends not only on the nanoadditive content, but also on the type of modifier used to change the MMT properties from hydrophilic to organophilic. It has been found that the exfoliation of MMT depends on the chemical structure of its modifier. The exfoliation takes place when MMT is modified with aminododecane acid. © 2007 Wiley Periodicals, Inc. J Appl Polym Sci, 2007
Some antiphospholipid antibodies recognize conformational epitopes shared by β2‐glycoprotein I and the homologous catalytic domains of several serine proteases
Authors: Lin Wei‐Shiang , Chen Pei‐Chih , Yang Cheng‐De , Cho EunJung , Hahn Bevra H. , Grossman Jennifer , Hwang Kwan‐Ki , Chen Pojen P. 
Published: April 2007

AbstractObjectiveTo test the hypothesis that some antiphospholipid antibodies (aPL) in patients with the antiphospholipid syndrome (APS) recognize a conformational epitope shared by β2‐glycoprotein I (β2GPI; the major autoantigen for the antiphospholipid antibodies) and the homologous catalytic domains of several serine proteases (such as thrombin, activated protein C [APC], and plasmin) involved in hemostasis.MethodsWe generated 4 new IgG monoclonal aPL (2 screened against β2GPI, 1 against thrombin, and 1 against protein C) from 2 APS patients. The monoclonal antibodies (mAb) were analyzed for binding to β2GPI, thrombin, APC, and plasmin, as well as for anticardiolipin antibody (aCL) activity. To demonstrate a shared epitope between β2GPI and a serine protease, 1 mAb was studied by cross‐inhibition analysis.ResultsBoth of the IgG anti‐β2GPI mAb bound to thrombin, APC, and plasmin. On the other hand, the 1 anti‐thrombin mAb and the 1 anti–protein C mAb also bound to β2GPI. Moreover, the binding of 1 cross‐reactive mAb to β2GPI was inhibited by α‐thrombin (which contains only the catalytic domain of thrombin). All 4 mAb displayed aCL activity.ConclusionTaken together with the findings that some aCL bind to several serine proteases that participate in hemostasis and share homologous catalytic domains, these data demonstrate that some aCL in APS patients recognize one or more conformational epitopes shared by β2GPI and the catalytic domains of disease‐relevant serine proteases.
Plasmacytoid dendritic cells in inflamed muscle of patients with juvenile dermatomyositis
Authors: López de Padilla Consuelo M. , Vallejo Abbe N. , McNallan Kelly T. , Vehe Richard , Smith Stephen A. , Dietz Allan B. , Vuk‐Pavlovic Stanimir , Reed Ann M. 
Published: April 2007

AbstractObjectiveTo examine whether dendritic cells (DCs) are constituents of muscle inflammation in juvenile dermatomyositis (DM).MethodsThe types, numbers, and activation state of DC subsets in inflamed muscle tissue from patients with juvenile DM and in noninflamed muscle tissue from control subjects were examined by multicolor immunofluorescence. Chemokine expression of the muscle‐infiltrating cells was examined by laser capture microdissection and quantitative polymerase chain reaction.ResultsPlasmacytoid DCs were the predominant component of the inflamed muscle tissue from patients with juvenile DM. These cells were identified by coexpression of CD4 and CD123, but not CD11c, and also expressed CD83, indicating maturity of the cells. In contrast, in noninflamed muscle, plasmacytoid DCs were scarce and did not express CD83. Mononuclear cells surrounding the blood vessels of inflamed muscle contained abundant transcripts of CCL19 and CCL21, but very little CCL18 transcripts. In contrast, cells from noninflamed muscle contained negligible amounts of CCL19 and CCL21, but had high amounts of CCL18. Both the inflamed and noninflamed muscle tissue had equivalent levels of CXCL12 transcripts, but inflamed muscle contained more transcripts of the CXCL12 receptor CXCR4.ConclusionThese findings are consistent with the idea that plasmacytoid DCs are mediators of muscle inflammation in juvenile DM. The abundance of CD83+ plasmacytoid DCs in perivascular areas and the overexpression of CCL19 and CCL21 in perivascular cellular foci suggest that in situ activation and maturation of resident plasmacytoid DCs are central to the initiation and perpetuation of muscle inflammation in juvenile DM.
The innate immune component ficolin 3 (Hakata antigen) mediates the clearance of late apoptotic cells
Authors: Honoré Christian , Hummelshoj Tina , Hansen Bjarke E. , Madsen Hans O. , Eggleton Paul , Garred Peter 
Published: April 2007

AbstractObjectiveFicolin 3 (Hakata antigen), a collagen‐like defense molecule, is a known autoantigen in patients with systemic lupus erythematosus (SLE). Recent studies have shown that other collagen‐like defense molecules, such as C1q, mannose‐binding lectin (MBL) and ficolin 2, bind to apoptotic cells and mediate their clearance by phagocytic cells. Dysfunction in this mechanism is regarded as an important contributor to the pathophysiology of SLE. Thus, we sought to determine whether ficolin 3 participates in the clearance of apoptotic cells.MethodsA Jurkat T cell line was used as the source of dying host cells. The cells were rendered apoptotic or necrotic by incubation with etoposide or by heat shocking, respectively. Binding of ficolin 3 to the cells was analyzed by flow cytometry. The apoptotic cells were incubated with human monocyte‐derived macrophages, and the effect of ficolin 3 on the adhesion/uptake was examined by flow cytometry.ResultsFicolin 3 bound to a population of late apoptotic cells, while a strong and uniform binding to necrotic cells was observed. The binding properties differed from those of MBL and ficolin 2. Ficolin 3 binding to late apoptotic cells resulted in a significant increase in adhesion/uptake by macrophages.ConclusionFicolin 3 mediates the clearance of late apoptotic cells, which suggests that this protein is involved in the maintenance of tissue homeostasis and might play a protective role against the development of autoimmunity.
Differential recognition of heat‐shock protein dnaJ–derived epitopes by effector and Treg cells leads to modulation of inflammation in juvenile idiopathic arthritis
Authors: Massa Margherita , Passalia Maristella , Manzoni Silvia Magni , Campanelli Rita , Ciardelli Laura , Yung Gisella Puga , Kamphuis Sylvia , Pistorio Angela , Meli Valentina , Sette Alessandro , Prakken Berent , Martini Alberto , Albani Salvatore 
Published: April 2007

AbstractObjectiveTo identify epitopes on Escherichia coli heat‐shock protein (HSP) dnaJ or on homologous human HSP dnaJ involved in the induction/modulation of autoimmune inflammation in patients with oligoarticular juvenile idiopathic arthritis (JIA).MethodsWe used a proliferation assay and cytokine production to evaluate the immune responses of synovial fluid mononuclear cells (SFMCs) to pan–HLA–DR binder peptides derived from either homologous or nonhomologous regions on bacterial and human HSP dnaJ. Cytofluorometric analysis was performed in order to phenotype and sort Treg cells. Sorted cells were then analyzed for the expression of the forkhead box P3 (FoxP3) transcription factor, and their regulatory capacity was tested in coculture assays.ResultsT cell responses to E coli HSP dnaJ–derived peptides were eminently proinflammatory. Conversely, peptides derived from human HSP dnaJ induced interleukin‐10 (IL‐10) production from SFMCs of patients with oligoarticular JIA. A positive correlation was found between disease with a better prognosis (persistent oligoarticular JIA) and recognition of 3 human HSP dnaJ–derived peptides. The recognition of the human peptide H134–148 also induced a significantly greater amount of IL‐10 in patients with persistent oligoarticular JIA than in those with extended oligoarticular JIA (P = 0.0012). Incubation of SFMCs from patients with persistent oligoarticular JIA with this human epitope increased the percentage of Treg cells and FoxP3 expression. It also induced the recovery of suppressor activity by Treg cells.ConclusionThis is the first description of a self‐regulating immune modulator circuit active during autoimmune inflammation through recognition of HSP epitopes with different functional properties. These epitopes induce T cells with regulatory function. Such induction correlates with disease severity and prognosis.
Impact of oral cyclophosphamide on health‐related quality of life in patients with active scleroderma lung disease: Results from the scleroderma lung study
Authors: Khanna Dinesh , Yan Xiaohong , Tashkin Donald P. , Furst Daniel E. , Elashoff Robert , Roth Michael D. , Silver Richard , Strange Charlie , Bolster Marcy , Seibold James R. , Riley David J. , Hsu Vivien M. , Varga John , Schraufnagel Dean E. , Theodore Arthur , Simms Robert , Wise Robert , Wigley Fredrick , White Barbara , Steen Virginia , Read Charles , Mayes Maureen , Parsley Ed , Mubarak Kamal , Connolly M. Kari , Golden Jeffrey , Olman Mitchell , Fessler Barri , Rothfield Naomi , Metersky Mark , Clements Philip J. ,   Scleroderma Lung Study Group
Published: April 2007

AbstractObjectiveTo assess the impact of cyclophosphamide (CYC) on the health‐related quality of life (HRQOL) of patients with scleroderma after 12 months of treatment.MethodsOne hundred fifty‐eight subjects participated in the Scleroderma Lung Study, with 79 each randomized to CYC and placebo arms. The study evaluated the results of 3 measures of health status: the Short Form 36 (SF‐36), the Health Assessment Questionnaire (HAQ) disability index (DI), and Mahler's dyspnea index, and the results of 1 preference‐based measure, the SF‐6D. The differences in the HRQOL between the 2 groups at 12 months were calculated using a linear mixed model. Responsiveness was evaluated using the effect size. The proportion of subjects in each treatment group whose scores improved at least as much as or more than the minimum clinically important difference (MCID) in HRQOL measures was assessed.ResultsAfter adjustment for baseline scores, differences in the HAQ DI, SF‐36 role physical, general health, vitality, role emotional, mental health scales, and SF‐36 mental component summary (MCS) score were statistically significant for CYC versus placebo (P< 0.05). Effect sizes were negligible (<0.20) for all of the scales of the SF‐36, HAQ DI, and SF‐6D at 12 months. In contrast, a higher proportion of patients who received CYC achieved the MCID compared with placebo in the HAQ DI score (30.9% versus 14.8%), transitional dyspnea index score (46.4% versus 12.7%), SF‐36 MCS score (33.3% versus 18.5%), and SF‐6D score (21.3% versus 3.8%).ConclusionOne year of treatment with CYC leads to an improvement in HRQOL in patients with scleroderma lung disease.
Involvement of the constitutive complex formation of c‐Ski/SnoN with smads in the impaired negative feedback regulation of transforming growth factor β signaling in scleroderma fibroblasts
Authors: Jinnin Masatoshi , Ihn Hironobu , Mimura Yoshihiro , Asano Yoshihide , Tamaki Kunihiko 
Published: April 2007

AbstractObjectiveThe principal effect of transforming growth factor β1 (TGFβ1) on mesenchymal cells is its stimulation of extracellular matrix synthesis. Previous reports indicated the significance of the autocrine TGFβ loop in the pathogenesis of scleroderma. The aim of this study was to examine c‐Ski and SnoN, principal molecules in the negative regulation of TGFβ signaling, to further understand the autocrine TGFβ loop in scleroderma.MethodsLevels of expression of c‐Ski/SnoN on cultured normal and scleroderma fibroblasts were determined by Western blotting, Northern blotting, and immunohistochemical staining. To determine the protein–protein interaction between c‐Ski/SnoN, Smads, and p300, immunoprecipitation was performed. A transient transfection assay was performed to measure promoter activity of the α2(I) collagen gene and the 3TP‐Lux plasmid construct.ResultsScleroderma fibroblasts exhibited increased c‐Ski/SnoN levels compared with normal fibroblasts, both in vivo and in vitro. Although c‐Ski/SnoN constitutively formed a complex with Smads by immunoprecipitation, the inhibitory effect of c‐Ski/SnoN on the promoter activity of human α2(I) collagen and 3TP‐Lux was impaired in scleroderma fibroblasts. Immunoprecipitation analyses also revealed that overexpressed c‐Ski/SnoN could not compete with p300 in these cells.ConclusionThese results indicate that impaired competition with p300 is the possible cause of dysfunction of c‐Ski/SnoN in scleroderma fibroblasts and that this might contribute to maintenance of the autocrine TGFβ loop in this disease.
Cyclin‐dependent kinase inhibition limits glomerulonephritis and extends lifespan of mice with systemic lupus
Authors: Zoja Carla , Casiraghi Federica , Conti Sara , Corna Daniela , Rottoli Daniela , Cavinato Regiane A. , Remuzzi Giuseppe , Benigni Ariela 
Published: April 2007

AbstractObjectiveTo examine whether the cyclin‐dependent kinase (CDK) inhibitor seliciclib ameliorates autoimmune nephritis in (NZB × NZW)F1 mice.MethodsIn experiment 1, NZB × NZW mice received seliciclib (100 mg/kg or 200 mg/kg) or vehicle by gavage, beginning at age 2 months and ending at 8 months of age. In experiment 2, seliciclib (200 mg/kg) was administered alone or combined with low‐dose methylprednisolone, starting at age 5 months, when immune complex deposition in the kidney had already occurred. Animals were followed up until all vehicle‐treated mice died. In 2 additional groups of NZB × NZW mice treated with seliciclib or vehicle from 2 months of age until 5 months of age, splenocytes were isolated and tested ex vivo for T cell and B cell activity.ResultsSeliciclib, given at an early phase of disease, prolonged survival, delayed the onset of proteinuria and renal function impairment, and protected the kidney against glomerular hypercellularity, tubulointerstitial damage, and inflammation. Combining seliciclib with low‐dose methylprednisolone in mice with established disease extended the lifespan and limited proteinuria and renal damage more than treatment with either agent alone. Seliciclib limited immunologic signs of disease, reducing glomerular IgG and C3 deposits and levels of serum anti‐DNA antibodies. Moreover, it inhibited ex vivo T cell and B cell proliferative responses to polyclonal stimuli. T cell production of interferon‐γ and interleukin‐10 and B cell release of IgG2a were reduced by treatment with seliciclib.ConclusionThese findings suggest that CDK activity may be a useful target in the treatment of systemic lupus erythematosus. A direct immunomodulatory action of seliciclib on T cells and B cells may be one of the mechanisms underlying the beneficial effects.
Cultivation of Tropheryma whipplei from the synovial fluid in Whipple's arthritis
Authors: Puéchal Xavier , Fenollar Florence , Raoult Didier 
Published: April 2007

AbstractThis report describes a patient who presented with fever, weight loss, diarrhea, and adenopathy. At the time of presentation he had a 28‐year history of unusually severe destructive polyarthritis. Duodenal biopsy revealed periodic acid–Schiff–positive macrophages. Polymerase chain reaction studies showed positivity for Tropheryma whipplei in synovial fluid, synovial tissue, and lymph node specimens, and Whipple's disease was diagnosed. T whipplei was successfully cultivated from the synovial fluid by both cell culture and axenic culture. This strain (named ART1) was subcultured and subsequently established and genotyped. Antibiotic treatment was instituted in the patient, after which his symptoms remitted. These findings show for the first time that Whipple's arthritis may be, at least in some cases, a septic arthritis.
BAFF‐modulated repopulation of B lymphocytes in the blood and salivary glands of RITUXIMAB‐TREATED patients with Sjögren's syndrome
Authors: Pers Jacques‐Olivier , Devauchelle Valérie , Daridon Capucine , Bendaoud Boutahar , Berre Rozenn Le , Bordron Anne , Hutin Pascal , Renaudineau Yves , Dueymes Maryvonne , Loisel Séverine , Berthou Christian , Saraux Alain , Youinou Pierre 
Published: April 2007

AbstractObjectiveTreatment with rituximab depletes B cells from the peripheral blood (PB) and salivary glands (SGs) of patients with primary Sjögren's syndrome (SS). The purpose of this study was to track the repopulation of B cell subsets in PB as well as their subsequent homing into SGs in patients with primary SS treated with rituximab.MethodsA series of 4‐color flow cytometry experiments delineated B cell subsets in 15 patients with primary SS. All were tested on days 8 and 15 of treatment. Nine of the patients were followed up monthly for 10 months, and the remaining 6 patients were followed up monthly for 24 months. Enzyme‐linked immunosorbent assays were developed to measure serum levels of BAFF and rituximab. SGs were biopsied at the start of the study and 4 months after treatment in 15 patients, 12 months after treatment in 3 patients, and 24 months after treatment in 2 patients.ResultsBaseline serum levels of BAFF correlated inversely (r = −0.92, P < 5 × 10−4) with the duration of B cell depletion: the higher the BAFF levels, the shorter the duration of B cell depletion. Four B cell subsets repopulated the PB: plasmablasts (CD19+, CD5−,IgD−,CD38++), transitional type 1 (T1) B cells (CD19+,CD5+,IgD+,CD38++), mature Bm2 cells (CD19+,CD5+/−,IgD+,CD38+/−), and memory B cells (CD19+,CD5−,IgD−,CD38−). Increased numbers of Bm2 cells and decreased memory B cells reappeared with time. Sequential SG biopsies revealed that B cells were absent in these glands for 12 months: they were detected 24 months after rituximab treatment. Memory and T1 B cells were the first B cells identified locally.ConclusionThe timing of B cell repopulation is modulated by BAFF and is followed by reconstitution of the preexisting abnormalities.
Duodenal atresia in an infant with triple‐X syndrome: A new associated malformation in 47,XXX
Authors: Rolle Udo , Linse Barbara , Glasow Simone , Sandig Klaus Rainer , Richter Thomas , Till Holger 
Published: April 2007

AbstractBACKGROUND: An association between the triple‐X syndrome (47,XXX) and gastrointestinal malformations is extremely rare. Most 47,XXX patients present with a normal phenotype, but genitourinary malformations have been described. CASE: We report a case of a child with 47,XXX and duodenal atresia. Antenatal ultrasound scan showed a dilated fetal stomach and upper part of the duodenum (double bubble phenomenon) at 31 weeks of gestation in a 31‐year‐old woman with polyhydramnion. The amniotic fluid karyotype showed 47,XXX. After a scheduled delivery, duodenal atresia was confirmed and treated with duodeno‐duodenostomy. CONCLUSIONS: The possible association of gastrointestinal and genitourinary tract anomalies requires a detailed postnatal clinical investigation and ultrasonographic examination of the abdomen, retroperitoneum, and pelvis on all triple‐X syndrome patients. Birth Defects Research (Part A) 2007. © 2007 Wiley‐Liss, Inc.
Bemessungshilfen und Konstruktion bei geneigten Querkräften
Authors: Mark Peter , Birtel Veit , Stangenberg Friedhelm 
Published: April 2007

AbstractDargestellt wird das praktische Vorgehen der Querkraftbemessung bei geneigt zu den Querschnittshauptachsen angreifenden Querkräften (zweiachsige Querkraft). Dazu werden für Stahlbetonträger mit Rechteckquerschnitt die Widerstandsgleichungen für Zug‐ und Druckstrebentragfähigkeiten auf Grundlage von DIN 1045‐1 und EC 2 abgeleitet, verifiziert und in Bemessungsdiagrammen aufgearbeitet. Ein Beispiel zeigt die einfache Ermittlung erforderlicher Bügelbewehrungsmengen mit gleichzeitigem Nachweis der Druckstrebentragfähigkeit. Die konstruktiven Regeln für Bügelverankerungen und das Versatzmaß lassen sich bei Beachtung der räumlichen Neigung des Querkraftfachwerks und der verdrehten Nulllinienlage direkt auf Situationen geneigter Querkraftwirkungen übertragen.