bluuebunny/crossref_metadata_2025 huggingface dataset:
Mutations of mitochondrial DNA polymerase γA are a frequent cause of autosomal dominant or recessive progressive external ophthalmoplegia
Authors: Lamantea Eleonora , Tiranti Valeria , Bordoni Andreina , Toscano Antonio , Bono Francesco , Servidei Serena , Papadimitriou Alex , Spelbrink Hans , Silvestri Laura , Casari Giorgio , Comi Giacomo P. , Zeviani Massimo
Published: October 2002

One form of familial progressive external ophthalmoplegia with multiple mitochondrial DNA deletions recently has been associated with mutations in POLG1, the gene encoding pol γA, the catalytic subunit of mitochondrial DNA polymerase. We screened the POLG1 gene in several PEO families and identified five different heterozygous missense mutations of POLG1 in 10 autosomal dominant families. Recessive mutations were found in three families. Our data show that mutations of POLG1 are the most frequent cause of familial progressive external ophthalmoplegia associated with accumulation of multiple mitochondrial DNA deletions, accounting for approximately 45% of our family cohort.
Steady‐shear rheology properties of polydimethylsiloxane (PDMS) colloids as a new contrast agent for nuclear magnetic resonance imaging
Authors: Su Fu‐Hu , Shyu Shin‐Shing , Chen Yi‐Chen , Fu Ywu‐Jang
Published: October 2002

This work investigated the toxicity, the nuclear magnetic resonance (NMR) spectra, the NMR imaging, and the steady‐rheology properties concerning polydimethylsiloxane (PDMS) colloids. These experiments illustrate low toxicity, strong NMR signal intensity, as well as clear images, and render the colloids the potential application as contrast agent for gastrointestinal NMR imaging. The steady‐shear rheology data are fitted very well by the model τ = τ0 + AÝm. According to the theory of Princen and Kiss, 12 we found the yield stresses (τ0) of the colloids are proportional to φ1/3/D in 0.72 ≦ φ ≦ 0.81. Based on the model and the definition of the capillary number Ca = τ/(σ/R), a linear relationship between log(D) and m was discovered if the assumptions that 2Ca σ/A and Ýeff are constants are satisfied. We also proved these assumptions are rational in the investigated range 0.62 ≦ φ ≦ 0.81. © 2002 Wiley Periodicals, Inc. J Appl Polym Sci 85: 1888–1896, 2002
Interference between reactants in simultaneous interpenetrating polymer network formation. II. Influence of the presence of a free‐radical initiator on polyurethane formation
Authors: Tabka Mohamed Tahar , Widmaier Jean‐Michel
Published: October 2002

Polyether polyurethane networks were prepared in solution at 25 and 60°C, using various organotin catalysts. The presence of a free‐radical initiator [viz. azobisisobutyronitrile (AIBN)] in the reaction media has no effect on the catalytic efficiency of organotin(IV) compounds, whereas it causes severe deactivation of organotin(II) compounds. This effect was explained by the following mechanism: formation of a cyclic 1 : 1 complex by coordination of the nitrile groups of AIBN with the tin(II) atom, which both reduces the effective catalyst concentration and allows the early decomposition into radicals, as previously seen, leading to tin oxidation. The addition of a free‐radical scavenger such as 3‐tert‐butyl pyrocatechol allows the maintenance of the catalyst efficiency of organotin(II) compounds at their reference level. © 2002 Wiley Periodicals, Inc. J Appl Polym Sci 85: 1929–1937, 2002
Tribological properties of SiO2 nanoparticle filled–phthalazine ether sulfone/phthalazine ether ketone (50/50 mol %) copolymer composites
Authors: Shao Xin , Tian Jun , Liu Weimin , Xue Qunji , Ma Chunlin
Published: October 2002

SiO2 nanoparticle filled–poly(phthalazine ether sulfone ketone) (PPESK) composites with various filler volume fractions were made by heating compression molding. The tribological behavior of the PPESK composites was investigated using a block‐on‐ring test rig by sliding PPESK‐based composite blocks against a mild carbon steel ring. The morphologies of the worn composite surfaces, wear debris, and the transferred films formed on the counterpart steel surface were examined with a scanning electron microscope, whereas the chemical state of the Fe element in the transfer film was analyzed with X‐ray photoelectron spectroscopy. In addition, IR spectra were taken to characterize the structure of wear debris and PPESK composites. It was found that SiO2 nanoparticle filled–PPESK composites exhibit good wear resistance and friction‐reduction behavior. The friction and wear behavior of the composites was improved at a volume fraction between 4.2 and 14.5 vol % of the filler SiO2. The results based on combined SEM, XPS, and IR techniques indicate that SiO2 nanoparticle filled–PPESK composite is characterized by slight scuffing in dry sliding against steel and polishing action between composite surface and that of the countpart ring, whereas unfilled PPESK is characterized by severe plastic deformation and adhesion wear. In the former case a thin, but not complete, transfer film was formed on the surface of the counterpart steel, whereas in the latter case, a thick and lumpy transfer film was formed on the counterpart steel surface. This accounts for the different friction and wear behavior of unfilled PPESK and SiO2 nanoparticle filled–PPESK composites. © 2002 Wiley Periodicals, Inc. J Appl Polym Sci 85: 2136–2144, 2002
Rheological behavior of N,N‐dimethyl acrylamide–acrylamido methylpropane sulphonate copolymer
Authors: Sabhapondit Anupom , Sarmah Anujjal , Borthakur Arun , Haque Inamul
Published: October 2002

Copolymer of N,N‐dimethylacrylamide (NNDAM) and sodium 2‐acrylamido‐2‐methylpropanesulfonate (NaAMPS) have been prepared by free‐radical copolymerization and characterized with the help of molecular weight, molecular weight distribution, intrinsic viscosity, and monomer ratio in the copolymer. The solution behavior of a copolymer containing 26.62 wt % NaAMPS is studied in different solvents, namely, water (W), dimethyl sulfoxide (DMSO), ethylene glycol (EG), and ethanol (EtOH). The reduced viscosity of the copolymer is highly dependent on the ionic strength of the copolymer solution. The reduced viscosity decreases as a function of solvent selection in the order W > DMSO > EtOH > EG. The shapes of the ηsp / C vs. C plots indicate the polyelectrolyte behavior of the copolymer, except for the case of EG solutions, where nonpolyelectrolyte behavior is observed. However, at a certain degree of ionization attained by adding W as cosolvent, the copolymer begins to demonstrate polyelectrolyte behavior. For this copolymer, there exists a minimum concentration of brine (NaCl, CaCl2, etc.) above which solution viscosity is not further reduced. The copolymer solution behaves as a power law fluid, and exhibits time‐dependent thixotropic behavior. The copolymer cannot regain its solution viscosity when allowed to shear at a constant rate for long period of time. The reduced viscosities of copolymer solutions increase with increasing temperature in W and DMSO, yet decreases with increasing temperature in EG. © 2002 Wiley Periodicals, Inc. J Appl Polym Sci 85: 1521–1529, 2002
Preparation of ultrahigh molecular weight syndiotactic poly(vinyl alcohol) microfibrillar fibers by low‐temperature solution polymerization of vinyl pivalate in tertiary butyl alcohol and saponification
Authors: Lyoo Won Seok , Kim Sam Soo , Ghim Han Do , Kim Jae Pil , Lee Sang‐Seob
Published: October 2002

Vinyl pivalate (VPi) was solution polymerized in tertiary butyl alcohol (TBA) and in dimethyl sulfoxide (DMSO) with a low chain transfer constant using a low temperature initiator, 2,2′‐azobis(2,4‐ dimethylvaleronitrile) (ADMVN). The effects of polymerization temperature and initiator concentration were investigated in terms of polymerization behavior and molecular structures of poly(vinyl pivalate) (PVPi) and its saponification product poly(vinyl alcohol) (PVA). TBA was absolutely superior to DMSO in increasing the syndiotacticity and molecular weight of PVA. In contrast, TBA was inferior to DMSO in causing conversion to polymer, indicating that the initiation rate of VPi production in TBA was lower than that in DMSO. These effects could be explained by a kinetic order of ADMVN concentration, calculated by the initial rate method. Low‐temperature solution polymerization of VPi in TBA or DMSO by adopting ADMVN proved to be successful in obtaining PVA of ultrahigh molecular weight [maximum number‐average degree of polymerization (Pn): 13,500–17,000] and of high yield (ultimate conversion of VPi into PVPi: 55–83%). In the case of bulk polymerization of VPi at the same conditions, maximum Pn and conversion were 14,500–17,500 and 22–36%, respectively. The Pn and syndiotactic diad content were much higher and the degree of branching was lower with PVA prepared from PVPi polymerized at lower temperatures in TBA. Moreover, PVA from the TBA system was fibrous, with a high degree of orientation of the crystallites, indicating the syndiotactic nature of TBA polymerization. © 2002 Wiley Periodicals, Inc. J Appl Polym Sci 85: 1992–2003, 2002
The effect of epoxy excess on the kinetics of an epoxy–anhydride system
Authors: Mauri A. N. , Riccardi C. C.
Published: October 2002

The uncatalyzed cure of a commercial tetrafunctional epoxy monomer TGDDM (N,N,N′,N′‐tetraglycidyl‐4,4′‐diaminodiphenylmethane) with hexahydrophthalic anhydride (HHPA), using variable stoichiometric ratios is reported. The reaction was followed by differential scanning calorimetry (DSC). Two kinds of experiments were performed: (1) fresh samples were run at several heating rates, and (2) samples, precured a certain time in an oil bath at constant temperature (i.e., 80 to 120°C), were run at 10°C/min. Two peaks were observed in the case of the epoxy excess but only one for the stoichiometric formulation: the peak at low temperature was attributed to the epoxy copolymerization with the anhydride while the peak at high temperature was attributed to the epoxy homopolymerization. The catalytic effect of the OH groups present in the epoxy monomer on the copolymerization reaction was demonstrated by the decrease in the activation energy of the propagation step when increasing the epoxy excess. There is a catalytic effect of the copolymerization product on the homopolymerization reaction. Our simplest model, proposed previously for a catalyzed epoxy/anhydride system [J. Polym. Sci. Part B: Polym. Phys. Ed., 37, 2799 (1999)], can be used to fit both isothermal and dynamical kinetic data. © 2002 Wiley Periodicals, Inc. J Appl Polym Sci 85: 2342–2349, 2002
Properties of rubbery polymers for the recovery of hydrogen sulfide from gasification gases
Authors: Wilks Broderick , Rezac Mary E.
Published: October 2002

Polydimethyl siloxane (PDMS) and two polyether‐polyamide copolymers (trade name Pebax) were evaluated for their ability to transport and separate gasification gases. Specifically, the permeabilities of hydrogen, carbon monoxide, carbon dioxide, and hydrogen sulfide were evaluated at temperatures up to 200°C. The permeabilities of all gases were approximately ten times faster through the PDMS than the Pebax materials. The permeabilities through all materials at all temperatures evaluated were H2S > CO2 > H2 > CO. As the temperature increased, the permeabilities of all gases increased through the Pebax. Conversely, for PDMS, hydrogen and carbon monoxide permeabilites increased with temperature while those of H2S and CO2 decreased. The H2S/H2 selectivities ranges from 1.2 (PDMS at 200°C) to 10.3 (Pebax 2533 at 35°C). The activation energies for permeation of these polymer/penetrant pairs are reported. © 2002 Wiley Periodicals, Inc. J Appl Polym Sci 85: 2436–2444, 2002
Influences of nonionic poly(ethylene glycol) polymer PEG on electrokinetic and rheological properties of bentonite suspensions
Authors: Ece Ö. I. , Alemdar A. , Güngör N. , Hayashi S.
Published: October 2002

The determination of the electrokinetic properties of colloidal systems is very important for the chracterization of these systems. Colloidal systems have high adsorption performance due to the carrying of negative charges and the colloid structure. The control of the electrokinetic properties of the bentonite–water system are important not only from a technological point view; they are also important from a scientific point of view. Knowing the electrokinetic and rheological properties of bentonite minerals is important for the estimation of the behavior of clays under various environmental conditions. The purpose of this study was to interpret the effect of the nonionic poly(ethylene glycol) (PEG) polymer on electrokinetic and rheological properties. Zeta potential and viscosity measurements were done as a function of PEG molecular weights (400, 3000, and 8000) and their concentrations (2.5 × 10−5 to 1.25 × 10−2 mol/L). We interpreted the experimental data, taking into account these two parameters. X‐ray diffaction studies were done together with the electrokinetic and rheological measurements. © 2002 Wiley Periodicals, Inc. J Appl Polym Sci 86: 341–346, 2002
Histochemical and ultrastructural studies of cartilage resorption and acid phosphatase activity during antler growth in fallow deer (Dama dama)
Authors: Szuwart Thomas , Kierdorf Horst , Kierdorf Uwe , Clemen Günter
Published: October 2002

Cartilage resorption in forming primary fallow deer antlers was studied by histochemistry and electron microscopy. A high activity of tartrate‐resistant acid phosphatase (TRAP), a histochemical marker of skeletal resorbing cells, was first detected in cells located in the mesenchymal tissue separating the columns of hypertrophic cartilage. No cartilage resorption was observed in this region. Intense TRAP staining occurred in large multinucleated cells (identified as inactive osteoclasts) as well as in smaller cells (regarded as mononuclear osteoclast progenitors). On the basis of these findings it was concluded that this was the region where osteoclasts differentiated from progenitor cells. Further proximally, the mineralized cartilage was eroded by active osteoclasts that were located in Howship's lacunae and exhibited an intense TRAP staining. Electron microscopy showed that the cells identified as inactive osteoclasts lacked a polarized organization. In contrast, the active osteoclasts in the zone of cartilage resorption exhibited a typical polarized organization: the nuclei congregated near the basolateral cell surface, and there was a zone of deep membrane infoldings (ruffled border) surrounded by a clear zone at the apical cell pole adjacent to the resorption surface of the mineralized cartilage. The multinucleated cartilage‐resorbing cells of the forming antler thus exhibited the typical histochemical and morphological features of active mammalian osteoclasts. Low levels of TRAP activity were also observed in hypertrophic chondrocytes; however, the specificity and potential significance of this staining remain to be elucidated. Anat Rec 268:66–72, 2002. © 2002 Wiley‐Liss, Inc.
Geoarchaeology of the Milfield Basin, northern England; towards an integrated archaeological prospection, research and management framework
Authors: Passmore David G. , Waddington Clive , Houghton Stephen J.
Published: October 2002

This paper presents the results of geoarchaeological investigations undertaken on the valley floor of the Milfield Basin in Northumberland, northern England. The area has a regionally and nationally important archaeological record, including a series of major neolithic and Anglian settlements, but has hitherto lacked archaeological assessment and management guidelines appropriate to the wide range of late‐glacial and post‐glacial environmental settings in the basin. This project has used geomorphological techniques to delimit and classify a total of nine valley floor landform elements in terms of their geomorphology and their known and potential archaeological and palaeoenvironmental associations.

Terraced glaciodeltaic and glaciofluvial sand and gravel landforms comprise the oldest landform elements described here and have formed the primary regional focus for prehistoric and early historic settlement and associated subsistence and ritual activity. These landforms have experienced little post‐glacial geomorphological activity, but their multiperiod archaeological landscapes lie beneath a shallow soil cover and are vulnerable to land‐use activities that disturb terrace soils and underlying sediments. A second group of landform elements are of Holocene age and include localized surface peats, alluvial fans, colluvial deposits and extensive deposits of terraced alluvium. Archaeological landscapes in these environments may lie buried intact and unrecorded beneath protective covers of sediment although locally they may have been subject to erosion and reworking by fluvial and slope processes. Holocene alluviation may account, at least in part, for the paucity of recorded archaeology in these parts of the basin. However, peat and organic‐rich sedimentary sequences identified here (including four 14C dated peat sequences) offer an opportunity to elucidate the environmental context and land‐use histories of local prehistoric and early historic communities in the basin, and hence also should be regarded as an archaeological resource.

Discussion of landform elements and their archaeological associations is followed by a brief outline of evaluation criteria developed with the aim of ensuring effective long‐term management of archaeological and palaeoenvironmental resources. It is concluded that geoarchaeological analysis of landform elements may be considered central to development of frameworks intended to underpin future programmes of archaeological research and the development of cultural resource management and evaluation strategies. Copyright © 2002 John Wiley & Sons, Ltd.
Angiostatin gene transfer as an effective treatment strategy in murine collagen‐induced arthritis
Authors: Kim Jong‐Mook , Ho Seong‐Hyun , Park Eun‐Jin , Hahn Woong , Cho Hongchan , Jeong Jae‐Gyun , Lee Yun‐Woo , Kim Sunyoung
Published: October 2002

Objective

To determine the efficacy of local therapy with human angiostatin gene in murine collagen‐induced arthritis (CIA).

Methods

DBA/1 mice were immunized with bovine type II collagen. Before the onset of arthritis, NIH3T3 fibroblasts, transduced with angiostatin‐expressing retroviral vectors or control vectors, were transplanted into the knee cavity. The incidence of arthritis in the knee joints was evaluated histologically based on pannus formation and cartilage destruction. Paws were evaluated macroscopically for redness, swelling, and deformities and immunologically for levels of interleukin‐1β. Angiogenesis in paws and knee joints was studied by immunohistochemistry using anti‐CD31 antibody and measurement of von Willebrand factor levels.

Results

Pannus formation and cartilage erosion were dramatically reduced in knees transplanted with angiostatin‐expressing cells. In addition, the onset of CIA in the ipsilateral paws below the knees injected with the angiostatin gene was significantly prevented. Furthermore, angiostatin gene transfer inhibited arthritis‐associated angiogenesis.

Conclusion

Local production of angiostatin in the knee was able to prevent the onset of CIA not only in the knee injected with genetically engineered cells, but also in the uninjected ipsilateral paw. This suggests that transfer of the angiostatin gene, and potentially also its protein, may provide a new, effective approach to the treatment of rheumatoid arthritis.
Cyclosporine inhibition of vascular endothelial growth factor production in rheumatoid synovial fibroblasts
Authors: Cho Mi‐La , Cho Chul‐Soo , Min So‐Youn , Kim Seung‐Hoon , Lee Shin‐Seok , Kim Wan‐Uk , Min Do‐June , Min Jun‐Ki , Youn Jeehee , Hwang Sue‐Yun , Park Sung‐Hwan , Kim Ho‐Youn
Published: October 2002

Objective

To determine the antiangiogenic effect of cyclosporin A (CSA) in rheumatoid arthritis (RA).

Methods

We investigated the effect of CSA on the production of vascular endothelial growth factor (VEGF) by rheumatoid synovial fibroblasts. Fibroblast‐like synoviocytes (FLS) were prepared from the synovial tissues of RA patients, and cultured in the presence of CSA. The production of VEGF by FLS was measured in culture supernatants by enzyme‐linked immunosorbent assay. The VEGF messenger RNA (mRNA) expression and activator protein 1 (AP‐1) binding activity for VEGF transcription were determined by polymerase chain reaction and electrophoretic mobility shift assay, respectively.

Results

CSA dose‐dependently inhibited both constitutive and transforming growth factor β‐induced VEGF production at the protein and mRNA levels. The suppressive action of CSA on VEGF synthesis was calcineurin dependent, as evidenced by a comparable inhibition by FK‐506. Agonists of cAMP, 3‐isobutyl‐1‐methylxanthine and N‐2‐O‐dibutyryl‐cAMP, mimicked the effect of CSA on VEGF production, while a cAMP antagonist, 2′,3′‐dideoxyadenosine, abrogated the effect of CSA. A gel mobility shift assay showed that the inhibitory effect of CSA was associated with decreased AP‐1 binding activity to the VEGF promoter, in a cAMP‐dependent manner.

Conclusion

CSA may exert an antiangiogenic effect by inhibiting AP‐1‐mediated VEGF expression in rheumatoid synovial fibroblasts.
Viral interleukin‐10 gene inhibition of inflammation, osteoclastogenesis, and bone resorption in response to titanium particles
Authors: Carmody Emily E. , Schwarz Edward M. , Puzas J. Edward , Rosier Randy N. , O'Keefe Regis J.
Published: October 2002

Objective

To evaluate the potential of viral interleukin‐10 (vIL‐10) gene therapy as an approach to prevent wear debris–induced inflammation, osteoclastogenesis, and bone resorption as it relates to periprosthetic osteolysis in patients with total joint replacements.

Methods

Replication‐defective adenovirus vectors expressing vIL‐10 (AdvIL‐10) or LacZ (AdLacZ) target genes were used to transduce fibroblast‐like synoviocytes (FLS) in vitro, and the effects of these cells on wear debris–induced proinflammatory cytokine production and receptor activator of nuclear factor κB ligand + macrophage colony‐stimulating factor splenocyte osteoclastogenesis were assessed by enzyme‐linked immunosorbent assay and tartrate‐resistant acid phosphatase assay. The effects of AdvIL‐10 administration on wear debris–induced osteolysis in vivo were analyzed using the mouse calvaria model, in which AdLacZ was used as the control.

Results

In the presence of AdLacZ‐infected FLS, titanium particle–stimulated macrophages exhibited a marked increase in secretion of tumor necrosis factor α (TNFα) (6.5‐fold), IL‐6 (13‐fold), and IL‐1 (5‐fold). Coculture with AdvIL‐10–transduced FLS suppressed cytokine secretion to basal levels, while addition of an anti–IL‐10 neutralizing antibody completely blocked this effect. The vIL‐10–transduced FLS also inhibited osteoclastogenesis 10‐fold in an anti–IL‐10–sensitive manner. In vivo, titanium implantation resulted in a 2‐fold increase in osteoclasts (P < 0.05) and in a 2‐fold increase in sagittal suture area (P < 0.05). This increase over control levels was completely blocked in mice receiving intraperitoneal injections of AdvIL‐10, all of whom had measurable serum vIL‐10 levels for the duration of the experiment. Immunohistochemistry demonstrated reduced cyclooxygenase 2 and TNFα expression in AdvIL‐10–infected animals.

Conclusion

This study demonstrates that gene delivery of vIL‐10 inhibits 3 processes critically involved in periprosthetic osteolysis: 1) wear debris–induced proinflammatory cytokine production, 2) osteoclastogenesis, and 3) osteolysis.
Fcγ receptor gene polymorphisms in Japanese patients with systemic lupus erythematosus: Contribution of FCGR2B to genetic susceptibility
Authors: Kyogoku Chieko , Dijstelbloem Hilde M. , Tsuchiya Naoyuki , Hatta Yoko , Kato Hitoshi , Yamaguchi Akihiro , Fukazawa Toru , Jansen Marc D. , Hashimoto Hiroshi , van de Winkel Jan G. J. , Kallenberg Cees G. M. , Tokunaga Katsushi
Published: October 2002

Objective

Human low‐affinity Fcγ receptors (FcγR) constitute a clustered gene family located on chromosome 1q23, that consists of FcγRIIA, IIB, IIC, IIIA, and IIIB genes. FcγRIIB is unique in its ability to transmit inhibitory signals, and recent animal studies demonstrated a role for FcγRIIB deficiency in the development of autoimmunity. Genetic variants of FcγRIIA, IIIA, and IIIB and their association with systemic lupus erythematosus (SLE) have been extensively studied in various populations, but the results were inconsistent. To examine the possibility that another susceptibility gene of primary significance exists within the FcγR region, we screened for polymorphisms of the human FCGR2B gene, and examined whether these polymorphisms are associated with SLE.

Methods

Variation screening of FCGR2B was performed by direct sequencing and polymerase chain reaction (PCR)‐single‐strand conformation polymorphism methods using complementary DNA samples. Genotyping of the detected polymorphism was done using genomic DNA, with a specific genotyping system based on nested PCR and hybridization probing. Association with SLE was analyzed in 193 Japanese patients with SLE and 303 healthy individuals. In addition, the same groups of patients and controls were genotyped for the previously known polymorphisms of FCGR2A, FCGR3A, and FCGR3B.

Results

We detected a single‐nucleotide polymorphism in FCGR2B, (c.695T>C), coding for a nonsynonymous substitution, Ile232Thr (I232T), within the transmembrane domain. The frequency of the 232T/T genotype was significantly increased in SLE patients compared with healthy individuals. When the same patients and controls were also genotyped for FCGR2A‐131R/H, FCGR3A‐176V/F, and FCGR3B‐NA1/2 polymorphisms, FCGR3A‐176F/F showed significant association. Two‐locus analyses suggested that both FCGR2B and FCGR3A may contribute to SLE susceptibility, while the previously reported association of FCGR3B was considered to be secondary and derived from strong linkage disequilibrium with FCGR2B.

Conclusion

These results demonstrate the association of a new polymorphism of FCGR2B (I232T) with susceptibility to SLE in the Japanese.
Autoantibody to c‐Mpl (thrombopoietin receptor) in systemic lupus erythematosus: Relationship to thrombocytopenia with megakaryocytic hypoplasia
Authors: Kuwana Masataka , Okazaki Yuka , Kajihara Mikio , Kaburaki Junichi , Miyazaki Hiroshi , Kawakami Yutaka , Ikeda Yasuo
Published: October 2002

Objective

To examine the prevalence, clinical associations, and pathogenic role of autoantibodies to c‐Mpl, the thrombopoietin (TPO) receptor, in patients with systemic lupus erythematosus (SLE).

Methods

Sera from 69 SLE patients, 84 patients with idiopathic thrombocytopenic purpura (ITP), and 60 healthy individuals were screened for anti–c‐Mpl antibodies by enzyme‐linked immunosorbent assay using recombinant c‐Mpl as an antigen. Clinical findings, autoantibody profiles, and serum TPO levels were compared between SLE patients with and without anti–c‐Mpl antibodies. A pathogenic role for the anti–c‐Mpl antibody was evaluated by examining its inhibitory effect on TPO‐dependent cell proliferation and megakaryocyte colony formation.

Results

Serum anti–c‐Mpl antibody was detected in 8 SLE patients (11.6%) and 7 ITP patients (8.3%), but in none of the healthy controls. Anti–c‐Mpl antibody was associated with thrombocytopenia (P = 0.0002) and a decrease in bone marrow megakaryocytes (P = 0.02) in SLE patients. Serum TPO levels in thrombocytopenic SLE patients with anti–c‐Mpl antibodies were significantly elevated compared with levels in those without the antibodies (P = 0.007). IgG fractions purified from anti–c‐Mpl antibody–positive sera bound to c‐Mpl expressed on the cell surface and inhibited TPO‐dependent cell proliferation and megakaryocyte colony formation.

Conclusion

Autoantibody to c‐Mpl is present in a subset of SLE patients with thrombocytopenia and megakaryocytic hypoplasia. It is likely that the impaired thrombopoiesis in these patients is mediated by the anti–c‐Mpl antibody, which functionally blocks an interaction between TPO and c‐Mpl.
Sites of collagenase cleavage and denaturation of type II collagen in aging and osteoarthritic articular cartilage and their relationship to the distribution of matrix metalloproteinase 1 and matrix metalloproteinase 13
Authors: Wu William , Billinghurst R. Clark , Pidoux Isabelle , Antoniou John , Zukor David , Tanzer Michael , Poole A. Robin
Published: October 2002

Objective

To determine the sites of cleavage and denaturation of type II collagen (CII) by collagenase(s) in healthy and osteoarthritic (OA) human articular cartilage and their relationship to the distribution of matrix metalloproteinase 1 (MMP‐1) and MMP‐13.

Methods

Single (per subject) full‐depth specimens from femoral condylar cartilage were isolated from articulating surfaces at autopsy from 8 subjects without arthritis and during arthroplasty from 10 patients with OA. Fixed frozen sections of cartilage were examined by immunoperoxidase localization, using antibodies to the collagenase‐generated cleavage site in CII, to an intrachain epitope recognized only in denatured CII, and to MMP‐1 and MMP‐13 (proenzyme, activated enzyme, or enzyme/inhibitor complex).

Results

Staining for collagen cleavage, denaturation, and both MMPs was weak to moderate and was frequently observed in pericellular sites in cartilage from younger, nonarthritic subjects. In specimens from older subjects, this staining was often more widespread and of greater intensity. Similar staining was usually, but not always, seen for all antibodies. In OA cartilage, staining was often stronger and more intense than that in normal cartilage from older subjects, and the distribution of staining was often similar for the different antibodies. Pericellular staining in the deep zone was frequently more pronounced in arthritic cartilage and extended to territorial and sometimes interterritorial sites. In very degenerate specimens, staining was distributed throughout most of the cartilage matrix.

Conclusion

These observations provide evidence for the presence of limited cleavage and denaturation of CII restricted to mainly pericellular and superficial sites in cartilage from younger, healthy subjects, where MMP‐1 and MMP‐13 are also selectively localized. Collagen degradation is more extensive and often more pronounced in cartilage from older, nonarthritic subjects. Characteristic changes in early OA are similar to those seen with aging in cartilage from older, healthy subjects, with collagen damage and collagenases concentrated closer to the articular surface. There was usually a close correspondence between the cleavage and denaturation of CII and the sites at which these collagenases were detected, suggesting that both MMPs are involved in the physiology and pathology. There was no evidence that the damage to CII is ordinarily initiated in sites other than at and near the articular surface and around chondrocytes.
Single‐nucleotide polymorphisms in tumor necrosis factor receptor genes: Definition of novel haplotypes and racial/ethnic differences
Authors: Bridges S. Louis , Jenq Grace , Moran Molly , Kuffner Tamara , Whitworth William C. , McNicholl Janet
Published: October 2002

Objective

To characterize allele frequencies of known single‐nucleotide polymorphisms (SNPs) in tumor necrosis factor receptor (TNFR) genes in African Americans with rheumatoid arthritis (RA), healthy African Americans, and healthy Caucasians.

Methods

One TNFRSF1B SNP (196 G/T) that influences susceptibility to familial RA in Caucasians and 3 SNPs in the 5′ flanking region of the TNFRSF1A gene (‐609G/T, ‐580A/G, and ‐383A/C) were genotyped in 108 African Americans with RA, 62 healthy African Americans, and 59 healthy Caucasians.

Results

There were no differences in TNFRSF1A allele frequencies between African Americans with RA and healthy African Americans. Allele frequencies were strikingly different, however, between healthy African Americans and healthy Caucasians: 0.13 versus 0.42 for ‐609T, 0.49 versus 0 for ‐580G, and 0.14 versus 0 for ‐383C. We identified 4 novel haplotypes defined by the 3 TNFRSF1A SNPs, the distribution of which was markedly different in healthy Caucasians and healthy African Americans (P = 0.000001 by chi‐square test‐. The frequencies of the TNFRSF1B 196 genotypes were similar in African Americans with RA and healthy African Americans but differed between healthy African Americans and healthy Caucasians (P = 0.05).

Conclusion

Although we observed no associations between known TNFR SNPs or haplotypes and RA, significant racial differences were observed at both loci. Comparison of these data with other published frequencies of TNFRSF1A and TNFRSF1B genotypes according to race suggests that the distribution in African American, Caucasian, and Asian populations differs significantly. These striking racial/ethnic differences in TNFR SNP frequencies may influence the likelihood of familial RA, severe disease, or response to TNF inhibitors and may have important evolutionary implications.
Anti–β2‐glycoprotein I antibodies in pediatric systemic lupus erythematosus and antiphospholipid syndrome
Authors: von Scheven Emily , Glidden David V. , Elder Melissa E.
Published: October 2002

Objective

To determine whether serum β2‐glycoprotein I antibody (anti‐β2GPI) detection improves identification of pediatric subjects at risk for antiphospholipid syndrome (APS).

Methods

Serum antiphospholipid antibodies (aPL) were identified by anticardiolipin enzyme‐linked immunosorbent assay (ELISA), lupus anticoagulant assays, and syphilis screening in children with primary APS, systemic lupus erythematosus (SLE), or SLE plus APS. Anti‐β2GPI level and isotype were determined by β2GPI ELISA and correlated with clinical manifestations and other aPL assays.

Results

One hundred‐ten subjects under 22 years of age and of mixed ethnicity were evaluated. Fifty‐seven had SLE (including 14 with APS), 25 had primary APS, 16 had SLE‐like APS, 6 were healthy children with aPL detected incidentally, 4 had other rheumatic diseases and 2 had other conditions. Anti‐β2GPI were detected in 48% of SLE subjects and did not improve aPL detection over standard tests. Anti‐β2GPI were associated with stroke (P = 0.014), but not with other APS manifestations, and were rarely detected in primary APS. Among subjects with APS manifesting as chronic thrombocytopenia, anti‐β2GPI distinguished subjects with SLE from those with primary APS.

Conclusions

With the exception of stroke, anti‐β2GPI detection does not improve identification of pediatric APS over that of traditional aPL assays. Anti‐β2GPI are rare in pediatric primary APS, but may predict evolution of chronic thrombocytopenia to SLE.
Racial differences in social network experience and perceptions of benefit of arthritis treatments among New York City Medicare beneficiaries with self‐reported hip and knee pain
Authors: Blake Valerie A. , Allegrante John P. , Robbins Laura , Mancuso Carol A. , Peterson Margaret G. E. , Esdaile John M. , Paget Stephen A. , Charlson Mary E.
Published: October 2002

Objective

To determine whether social network experience and perceptions of benefit of arthritis treatments influence the decision to seek diagnosis and treatment.

Methods

A population‐based telephone survey of 515 black and 455 white Medicare beneficiaries was conducted. Validated questionnaires adapted for use in a telephone interview were used to identify people with self‐reported symptoms of hip or knee pain. Treatment history for arthritis‐related pain and perceptions of benefit of treatment were also assessed.

Results

Forty‐two percent of blacks and 31% of whites reported hip or knee pain. Forty‐two percent of blacks and 65% of whites reported knowing someone who had surgery for hip or knee pain (P < 0.0001). Blacks were less likely than whites to report that surgery had helped someone they knew with hip or knee pain (not significant).

Conclusion

Blacks know fewer people who have had surgical treatment of hip and knee pain than whites and appear to be less likely to perceive that such treatment is beneficial.
Secular changes in the quality of published randomized clinical trials in rheumatology
Authors: Hill Catherine L. , LaValley Michael P. , Felson David T.
Published: October 2002

Objective

To assess the quality of published randomized clinical trials (RCTs) in rheumatology and to determine whether there has been improvement in quality between 2 time periods, 1987–1988 and 1997–1998.

Methods

Using MEDLINE and a hand search of selected rheumatology journals, we identified RCTs of adult rheumatic diseases published in English in 1987–1988 or 1997–1998. We examined trial quality with an expanded version of the Jadad scale, which assesses the adequacy of reported random sequence generation, allocation concealment, blinding, and analysis. All trials were read by 1 reviewer, with prior standardization using a random sample read by 2 reviewers. We also evaluated “high”‐ versus “low”‐impact journals based on citation index.

Results

Two hundred forty RCTs (1987–1988 119 RCTs, 1997–1998 121 RCTs) were assessed. Results showed improvement in the quality of the trials, but the rates of reported random sequence generation, allocation concealment, power, and intent‐to‐treat analyses were persistently low. Low rates of reports of random sequence generation, allocation concealment, and intent‐to‐treat analyses were present even in the high‐impact journals.

Conclusion

There has been improvement in the quality of reporting of RCTs in rheumatology between 1987–1988 and 1997–1998. However, methodologic problems such as lack of allocation concealment, inadequate random sequence generation, lack of reporting of power, and lack of intent‐to‐treat analyses remain common. Many of these problems are established sources of bias in RCTs and are easily rectifiable.
Facilitating community information seeking using the Internet: Findings from three public library–community network systems
Authors: Pettigrew Karen E. , Durrance Joan C. , Unruh Kenton T.
Published: October 2002

We report findings from a recent study of how public libraries are using on‐line community networks to facilitate the public's information seeking and use in everyday situations. These networks have been lauded for their potential to strengthen physical communities through increasing information flow about local services and events, and through facilitating civic interaction. However, little is known about how the public uses such digital services and what barriers they encounter. This article presents findings from a 2‐year study that comprised a national survey with public library staff, followed by extensive case studies in three states. At each site, data were collected using on‐line surveys, field observation, in‐depth interviews, and focus groups with Internet users, human service providers, and library staff. The on‐line surveys and the follow‐up interviews with respondents were based on sense‐making theory. In our article we discuss: (1) how the public is using networked community information systems and the Internet for daily problem solving, (2) the types of barriers users encounter, and (3) the benefits for individuals and physical communities from public library–community networking initiatives and the emergence of “information communities.”
A cognitive‐emotional account of the shape of the probability weighting function
Authors: Brandstätter Eduard , Kühberger Anton , Schneider Friedrich
Published: October 2002

Research has shown a tendency of decision makers to overweight small probabilities and to underweight moderate and large probabilities. In standard treatments this is graphically modeled by an inverse S‐shaped probability weighting function. We suggest that emotions play a significant role in the shaping of the probability weighting function. In particular, the weighting function is proposed to be some function of objective probability, expected elation, and expected disappointment. The overweighting of small probabilities results from the anticipated elation after having won, given that winning was very unlikely. The underweighting of large probabilities results from anticipated disappointment after having failed to win, given that winning was very likely. Hence, probability is assumed to influence utility. Three experiments investigate these hypotheses. Experiments 1 and 2 show that a convex function relates probability to surprise. Experiment 3 elicits choice data and further supports the proposed hypotheses. The model adds to the understanding of the cognitive and emotional processes underlying the shape of the probability weighting function. Copyright © 2002 John Wiley & Sons, Ltd.
Common structural features of nucleic acid polymerases
Authors: Cramer P.
Published: October 2002

Structures of multisubunit RNA polymerases strongly differ from the many known structures of single subunit DNA and RNA polymerases. However, in functional complexes of these diverse enzymes, nucleic acids take a similar course through the active center. This finding allows superposition of diverse polymerases and reveals features that are functionally equivalent. The entering DNA duplex is bent by almost 90° with respect to the exiting template–product duplex. At the point of bending, a dramatic twist between subsequent DNA template bases aligns the “coding“ base with the binding site for the incoming nucleoside triphosphate (NTP). The NTP enters through an opening that is found in all polymerases, and, in most cases, binds between an α‐helix and two catalytic metal ions. Subsequent phosphodiester bond formation adds a new base pair to the exiting template–product duplex, which is always bound from the minor groove side. All polymerases may undergo “induced fit” upon nucleic acid binding, but the underlying conformational changes differ. BioEssays 24:724–729, 2002. © 2002 Wiley Periodicals, Inc.
Selectivity in heavy metal‐ binding to peptides and proteins
Authors: DeSilva Tara M. , Veglia Gianluigi , Porcelli Fernando , Prantner Andrew M. , Opella Stanley J.
Published: October 2002

The metal‐binding affinities and three‐dimensional structures of three synthetic 18‐residue peptides with sequences derived from that of the highly conserved metal‐binding motif MXCXXC found in many heavy metal‐binding proteins were determined. A change in register of the cysteines and alanines of the sequence from the periplasmic mercury‐binding protein, MerP, i.e., CAAC, CACA, and CCAA, affects the specificity of metal binding, in particular, the peptide with vicinal cysteines binds only mercury. The three‐dimensional structures of the mercury‐bound forms of the three peptides determined in solution by NMR spectroscopy peptides differ considerably, even though they are all linear bicoordinate complexes. The three‐dimensional structure of the peptide with CAAC bound to Cd(II) demonstrates that the metal‐binding loop is malleable enough to accommodate modes of coordination other than linear bicoordinate. © 2002 Wiley Periodicals, Inc. Biopolymers 64: 189–197, 2002
Differential rates of gene expression monitored by green fluorescent protein
Authors: Lu Canghai , Albano C. Renee , Bentley William E. , Rao Govind
Published: October 2002

The use of green fluorescent protein (GFP) as a reporter gene has made a broad impact in several areas, especially in studies of protein trafficking, localization, and expression analysis. GFP's many advantages are that it is small, autocatalytic, and does not require fixation, cell disruption, or the addition of cofactors or substrates. Two characteristics of GFP, extreme stability and chromophore cyclization lag time, pose a hindrance to the application of GFP as a real‐time gene expression reporter in bioprocess applications. In this report, we present analytical methods that overcome these problems and enable the temporal visualization of discrete gene regulatory events. The approach we present measures the rate of change in GFP fluorescence, which in turn reflects the rate of gene expression. We conducted fermentation and microplate experiments using a protein synthesis inhibitor to illustrate the feasibility of this system. Additional experiments using the classic gene regulation of the araBAD operon show the utility of GFP as a near real‐time indicator of gene regulation. With repetitive induction and repression of the arabinose promoter, the differential rate of GFP fluorescence emission shows corresponding cyclical changes during the culture. © 2002 Wiley Periodicals, Inc. Biotechnol Bioeng 79: 429–437, 2002.
Successful management of a resistant renal artery stenosis in a child using a 4 mm cutting balloon catheter
Authors: Haas Nikolaus A. , Ocker Volker , Knirsch Walter , Holder Martin , Lochbuehler Helmut , Lewin Martin A.G. , Uhlemann Frank
Published: October 2002

Percutaneous transluminal renal angioplasty (PTRA) is a well‐established method to treat renal artery stenosis (RAS) in children and adults. However, a significant number of stenoses might not be treated by interventional techniques due to the inability to dilate the RAS. Conventional balloon angioplasty with a high‐pressure coronary angioplasty balloon at 20 atm was unable to dilate a significant RAS in a 12‐year‐old child with severe renovascular hypertension (RR 195/125 mm Hg). After using a 4 mm cutting balloon, we achieved wide patency of the renal artery and an instant normalization of blood pressure without further need of antihypertensive therapy. PTRA using the cutting balloon technique may offer an additional therapeutic option for selected patients in whom conventional balloon angioplasty was not able to dilate RAS. Cathet Cardiovasc Intervent 2002;56:227–231. © 2002 Wiley‐Liss, Inc.
Enantioselective photoreaction of achiral tropolone ether in inclusion crystals with optically active host compounds
Authors: Tanaka Koichi , Nagahiro Ryoji , Urbanczyk‐Lipkowska Zofia
Published: October 2002

Achiral 4‐isopropyltropolone methyl ether (3) included in an optically active host compound (−)‐1 yielded optically active photocyclization products (−)‐5 and (−)‐6 in 96 and 90% ee, respectively, upon photoirradiation in the solid state. Chirality 14:568–572, 2002. © 2002 Wiley‐Liss, Inc.
A problem‐solving approach to stress reduction among younger women with breast carcinoma
Authors: Allen Susan M. , Shah Ann C. , Nezu Arthur M. , Nezu Christine Maguth , Ciambrone Desirée , Hogan Joseph , Mor Vincent
Published: October 2002

BACKGROUND

Previous research indicates that younger women (i.e., ≤ 50) with breast carcinoma experience greater emotional distress than older women (i.e., > 50) and that coping style is significantly related to the psychosocial adjustment of women with this disease. The purpose of this study was to evaluate through a randomized controlled trial the effectiveness of a problem‐solving training intervention designed to empower women with breast carcinoma to cope with a range of difficulties when diagnosed in mid‐life.

METHODS

The study population consisted of women aged 50 years or younger who had no prior history of breast carcinoma, were diagnosed with Stage I‐IIIA tumors, and for whom a first course of chemotherapy had been initiated recently. The intervention consisted of two in‐person and four telephone sessions with an oncology nurse who provided problem‐solving skills training and informational materials to the women over a 12‐week period. All subjects were assessed for physical and psychosocial adjustment through telephone and mailed surveys at baseline, at 4 –months, and at 8 months.

RESULTS

Of 183 eligible women, 164 participated (a 90% participation rate), 149 of whom completed the study (a 91% completion rate). The subjects had significantly lower unmet needs and better mental health at the 4‐month assessment. The intervention significantly decreased the number and severity of difficulties experienced by women with average or good problem‐solving skills at 8 months, but was not effective in alleviating or resolving the problems encountered by women with poor problem‐solving skills, relative to the control group.

CONCLUSIONS

We conclude that this problem‐solving therapy‐based home care training intervention is an effective method of helping the majority of women with breast carcinoma to reduce the stresses associated with the diagnosis and treatment of cancer in mid‐life. Cancer 2002;94:3089–100. © 2002 American Cancer Society.

DOI 10.1002/cncr.10586