bluuebunny/crossref_metadata_2025_split huggingface dataset:
Antinuclear antibodies following infliximab treatment in patients with rheumatoid arthritis or spondylarthropathy
Authors: De Rycke Leen , Kruithof Elli , Van Damme Nancy , Hoffman Ilse E. A. , Van den Bossche Nancy , Van den Bosch Filip , Veys Eric M. , De Keyser Filip 
Published: April 2003

AbstractObjectiveTo investigate the effect of infliximab treatment on antinuclear antibodies (ANAs), anti–double‐stranded DNA (anti‐dsDNA), antinucleosome, antihistone, and anti–extractable nuclear antigen (anti‐ENA) antibodies in rheumatoid arthritis (RA) and spondylarthropathy (SpA) patients.MethodsSera from 62 RA and 35 SpA patients treated with infliximab were tested at baseline and week 30 (RA group) or week 34 (SpA group). ANAs were tested by indirect immunofluorescence (IIF) on HEp‐2 cells. Anti‐dsDNA antibodies were detected by IIF on Crithidia luciliae and by enzyme‐linked immunosorbent assay (ELISA) and were further isotyped with γ, μ, and α chain–specific conjugates at various time points. Antinucleosome antibodies were tested by ELISA. Antihistone and anti‐ENA antibodies were detected by line immunoassay.ResultsInitially, 32 of 62 RA patients and 6 of 35 SpA patients tested positive for ANAs. After infliximab treatment, these numbers shifted to 51 of 62 (P < 0.001) and 31 of 35 (P < 0.001), respectively. At baseline, none of the RA or SpA patients had anti‐dsDNA antibodies. After infliximab treatment, 7 RA patients (P = 0.016) and 6 SpA patients (P = 0.031) became positive for anti‐dsDNA antibodies. All 7 anti‐dsDNA–positive RA patients had IgM and IgA anti‐dsDNA antibodies. Three of the 6 anti‐dsDNA–positive SpA patients had IgM and IgA anti‐dsDNA antibodies, and 2 had IgM anti‐dsDNA antibodies alone. In both diseases, the IgM anti‐dsDNA antibodies appeared before the IgA anti‐dsDNA antibodies. During the observation period, no IgG anti‐dsDNA antibodies or lupus symptoms were observed. The development of antinucleosome, antihistone, or anti‐ENA antibodies following infliximab treatment was observed in some patients, but the numbers were not statistically significant.ConclusionInfliximab treatment may induce ANAs, and especially IgM and IgA anti‐dsDNA antibodies, in RA and SpA patients. However, no anti‐dsDNA IgG antibodies or lupus symptoms were observed during the period of observation in this study, and the development of antinucleosome, antihistone, or anti‐ENA antibodies was not statistically significant. These observations do not exclude potential induction of clinically significant lupus in the long term, and further followup is therefore mandatory.
Low prevalence of antibodies to glucose‐6‐phosphate isomerase in patients with rheumatoid arthritis and a spectrum of other chronic autoimmune disorders
Authors: Matsumoto Isao , Lee David M. , Goldbach‐Mansky Raphaela , Sumida Takayuki , Hitchon Carol A. , Schur Peter H. , Anderson Ronald J. , Coblyn Jonathan S. , Weinblatt Michael E. , Brenner Michael , Duclos Bernard , Pasquali Jean‐Louis , El‐Gabalawy Hani , Mathis Diane , Benoist Christophe 
Published: April 2003

AbstractObjectiveArthritis in the K/BxN mouse model results from pathogenic immunoglobulins that recognize glucose‐6‐phosphate isomerase (GPI), a glycolytic enzyme residing in the cytoplasm of all cells. Antibodies directed against GPI can, alone, transfer arthritis to healthy recipients. Previous experiments have revealed significant titers of anti‐GPI antibodies in the serum of many patients with rheumatoid arthritis (RA). We evaluated the generality of these observations in cohorts of patients with 12 different arthritic and chronic autoimmune diseases and in population‐matched healthy control subjects.MethodsAnti‐GPI antibodies were assayed in 811 individual serum samples by enzyme‐linked immunosorbent assay with 2 forms of GPI, recombinant and native. Results were confirmed by immunoblotting.ResultsSeveral patients had significantly elevated anti‐GPI antibody titers, but without the prevalence or the specificity reported previously. Only 15% of RA patients had anti‐GPI antibodies (range 12–29% in different cohorts), with a higher prevalence in patients with active disease. Psoriatic arthritis, undifferentiated arthritis, and spondylarthropathy patients also displayed anti‐GPI antibodies at similar frequencies (12–25%). Similar titers were detected in a proportion (5–10%) of control subjects or patients with Crohn's disease or sarcoidosis. Very high titers were found in rare cases of RA and systemic lupus erythematosus.ConclusionNo disease‐specific pattern of antibody positivity to GPI was apparent. While the antibody‐mediated mechanism at play in the mouse model may exemplify a generic mechanism for some forms of arthritis in humans, GPI itself does not appear to be a target common to the majority of RA patients.
Pathogenic T cells in murine lupus exhibit spontaneous signaling activity through phosphatidylinositol 3‐kinase and mitogen‐activated protein kinase pathways
Authors: Niculescu Florin , Nguyen Phuong , Niculescu Teodora , Rus Horea , Rus Violeta , Via Charles S. 
Published: April 2003

AbstractObjectiveTo determine the activation status of two cytoplasmic signaling pathways, phosphatidylinositol 3‐kinase (PI 3‐kinase) and the mitogen‐activated protein kinase (MAPK) family.MethodsWe studied the pathogenic CD4+ T cells that drive disease in the parent‐into‐F1 mouse model of lupus‐like chronic graft‐versus‐host disease (GVHD). We determined immunoprecipitated kinase activity for PI 3‐kinase and MAPK members (Raf‐1, extracellular signal–regulated kinase 1 [ERK‐1], c‐Jun N‐terminal kinase 1 [JNK‐1], and p38 MAPK) from either unfractionated splenocytes or purified donor CD4+ T cells. Uninjected normal mice served as negative controls, and acute GVHD mice served as positive controls.ResultsCompared with negative controls, unfractionated splenocyte kinase activity from chronic GVHD mice was significantly increased for PI 3‐kinase and JNK‐1, but not for Raf‐1, p38 MAPK, or ERK‐1. Increased PI 3‐kinase and JNK‐1 activity was also seen in acute GVHD splenocytes, as was increased Raf‐1 and p38 MAPK activity. The pattern of increased PI 3‐kinase and JNK‐1 activity seen in unfractionated chronic GVHD splenocytes was also seen in isolated donor, but not host, CD4+ T cells from chronic GVHD mice, indicating that donor CD4+ T cell signaling activity accounted for at least a portion of the activity observed in unfractionated splenocytes. Increased ERK‐1 activity was not seen in either donor or host CD4+ T cells. This pattern of cytoplasmic signaling pathway in donor CD4+ T cells was associated with increased T cell receptor membrane signaling activation (Lck and Fyn phosphorylation) and increased transcription activation (phosphorylation of inhibitor of nuclear factor κB), confirming the biologic significance of these observations.ConclusionThe pathogenic T cells driving disease in this murine model exhibit activation in the form of spontaneous cytoplasmic signaling pathway activity that can be detected without in vitro restimulation and involves a T cell–specific (PI 3‐kinase) and a nonspecific stress/cytokine pathway (JNK‐1). These results raise the possibility that a full characterization of the signaling pathways active in pathogenic lupus T cells might lead to new therapeutic targets.
Development of an instrument to measure disability in parenting activity among women with rheumatoid arthritis
Authors: Katz Patricia P. , Pasch Lauri A. , Wong Belinda 
Published: April 2003

AbstractObjectiveTo develop a method of assessing and summarizing parenting function and disability, and to use that method to describe parenting disability among a group of women with rheumatoid arthritis (RA).MethodsThe study group comprised 231 women with RA who are members of the University of California, San Francisco RA Panel Study. Parenting disability scales were developed by first asking open‐ended questions and then, based on the responses, constructing closed‐ended questions. Separate sets of questions were asked concerning young (ages 0–5 years) and older (ages 6–18 years) children. Parenting disability indices (PDIs), scored in a manner similar to that for the Health Assessment Questionnaire (HAQ) (range 0–3), were developed (total, and for young and older children). Associations of PDIs with demographic, health, and symptom measures were assessed.ResultsSubstantial proportions of women with RA experienced disability in parenting activities. Greater disability was reported for activities related to parenting young children. Doing less of parenting functions because of RA was commonly reported. The mean total PDI of women who currently had children under age 18 years, taking into account “doing less” of activities because of RA, was 0.76 (range 0–2.08). Greater parenting disability was associated with poorer general function (HAQ; P < 0.0001), more severe pain (P = 0.002), greater fatigue (P = 0.0005), greater parenting stress (P = 0.005), and greater psychological distress (depressive symptoms; P < 0.0001).DiscussionThe PDI appears to be valid. This method can provide the means of assessing parenting disability, its risk factors, and its effects, which may assist in identifying ways of helping individuals with RA cope more effectively with parenting.
Prevalence of antineutrophil cytoplasmic antibodies in patients with various pulmonary diseases or multiorgan dysfunction
Authors: Vassilopoulos Dimitrios , Niles John L. , Villa‐Forte Alexandra , Arroliga Alejandro C. , Sullivan Eugene J. , Merkel Peter A. , Hoffman Gary S. 
Published: April 2003

AbstractObjectiveTo determine the prevalence of antineutrophil cytoplasmic antibodies (ANCA) in patients with diseases that may mimic systemic vasculitides, such as severe multiorgan dysfunction (MOD) and parenchymal pulmonary disorders.MethodsWe conducted a prospective study of patients with MOD admitted to the medical intensive care unit and patients with various lung diseases seen at the outpatient pulmonary clinic of a tertiary care hospital. Patients with a documented diagnosis of Wegener's granulomatosis (WG) served as positive controls. ANCA were determined in serum samples from each patient by a combination of indirect immunofluorescence (IIF) and enzyme‐linked immunosorbent assays (ELISAs) for antibodies to proteinase‐3 and myeloperoxidase (anti‐MPO).ResultsNinety‐nine patients with MOD, 29 outpatients with various lung disorders, and 18 patients with WG were included in the study. ANCA were detected by IIF alone in 16% (15/96) of patients with nonvasculitic MOD and 17% (5/29) of outpatients with various pulmonary disorders. The majority of the positive IIF specimens from each group displayed an atypical IIF pattern (73% and 80%, respectively). Only 1 specimen from patients with nonvasculitic disorders was positive for anti‐MPO. ANCA by both IIF and ELISA were detected in 78% (12/14) of control patients with WG.ConclusionDetection of ANCA by the combination of IIF and antigen‐specific assays for proteinase 3 and myeloperoxidase in diseases that mimic systemic vasculitides is highly specific for WG, microscopic polyangiitis, and Churg‐Strauss syndrome.
Human immunodeficiency virus–associated polymyositis: A longitudinal study of outcome
Authors: Johnson Randall W. , Williams Francis M. , Kazi Salahuddin , Dimachkie Mazen M. , Reveille John D. 
Published: April 2003

AbstractObjectiveTo determine the clinical course and optimum treatment of human immunodeficiency virus (HIV)–associated myositis.MethodsSixty‐four patients attending a county outpatient HIV/acquired immunodeficiency syndrome facility were referred for the presence of elevated creatine kinase (CK) levels or muscle weakness. Patients underwent neurologic and rheumatologic evaluation, electromyography, and muscle biopsy after exclusion for recreational drug or alcohol use, metabolic/endocrine disorders, zidovudine therapy, and other infections.ResultsThirteen patients (20%) had biopsy‐proven myositis. The median duration of HIV infection prior to diagnosis of myositis was 4.3 years (range 0–11 years). Six patients had concomitant diffuse infiltrative lymphocytosis syndrome. There was no correlation of severity of weakness, stage of HIV infection, or retroviral treatment with the CK level at diagnosis. Eight patients received prednisone (60 mg/day) with 5 attaining complete resolution of myositis. The remaining 3 patients received immunosuppressive therapy (azathioprine or methotrexate and intravenous immunoglobulin) and had normalization of strength and CK. Four patients had spontaneous resolution of their myositis without treatment.ConclusionHIV‐associated myositis occurs at any stage of HIV infection, has a relatively good prognosis, responds well to immunosuppressive therapy, and has little evidence of adverse outcome on the HIV infection.
Study on the sorption properties of α1‐acid glycoprotein (AGP)‐based stationary phase modified by organic solvents
Authors: Gyimesi‐Forrás Krisztina , Szász György , Báthory Gábor , Mészáros György , Gergely András 
Published: April 2003

AbstractAn α1‐acid glycoprotein, immobilized on silica (Chiral‐AGP) is one of the most widely used chiral stationary phases for the enantiomeric separation of a wide variety of chiral drugs with several applications in the biological and clinical field. The aim of this work was to study the sorption properties of the AGP‐based stationary phase, which may have crucial importance for enantioselectivity. New binding data to the mechanism of the chromatographic separation are presented. The sorption of both organic solvents, i.e., acetonitrile and dioxane, shows remarkable pH dependency. A fluorescence quenching study was carried out to elucidate structural changes of AGP in the presence of acetonitrile using 2,2,2‐trichloroethanol as fluorescence quencher. Chirality 15:377–381, 2003. © 2003 Wiley‐Liss, Inc.
Chiral phospholene and phospholane chalcogenides: Stereochemistry and chiral recognition by multinuclear NMR spectroscopy of their Rh2[(R)‐MTPA]4 adducts
Authors: Magiera Damian , Moeller Stefan , Drzazga Zbigniew , Pakulski Zbigniew , Pietrusiewicz K. Michal , Duddeck Helmut 
Published: April 2003

AbstractFull NMR spectral assignments of the phospholene chalcogenides 1–12 are presented and their stereochemistry proven. The enantiomeric ratio of any of these compounds can be monitored easily by adding one mole equivalent of the chiral auxiliary Rh2[(R)‐MTPA]4 (MTPA‐H ≡ Mosher's acid) and subsequent NMR inspection. Some surprisingly large diastereomeric signal dispersion is observed in the 1H NMR spectra of the adducts, leading to the conclusion that intramolecular anisotropy interaction between groups inside the ligand molecules exists. The dependence of dispersion effects on the nature of the chalcogenide atom is investigated. Chirality 15:391–399, 2003. © 2003 Wiley‐Liss, Inc.
On the development of the stratification of the inner plexiform layer in the chick retina
Authors: Drenhaus Ulrich , Morino Patrizia , Veh Rüdiger W. 
Published: April 2003

AbstractThis study investigated the development of the subdivision of the chick inner plexiform layer (IPL). The approach included an immunohistological analysis of the temporal and spatial expressions of choline acetyltransferase, of the neural–glial‐related and neural–glial cell adhesion molecules (NrCAM and NgCAM, respectively) and axonin‐1, and of inwardly rectifying potassium (Kir) channels in 5‐ to 19‐day‐old (E5–E19) embryos. Ultrastructural investigations evaluated whether synaptogenesis accompanies the onset of differentiation of the IPL. We found that the differentiation of the IPL started at E9. Distinct cholinergic strata appeared, NrCAM immunoreactivity showed a poorly defined stratification, and Kir3.2 was expressed in the IPL and in the inner nuclear layer. From E10 until late E14, NgCAM‐ and axonin‐1–immunoreactive strata emerged in an alternating sequence from the outer to the inner IPL. During this period, the NrCAM pattern sharpened, and eventually five bands of weaker and stronger immunoreactivity were found. Conventional synapses formed at the beginning of E9, and stratification of the IPL also began on the same day at the same location. Synaptogenesis and stratification followed a gradient from the central to the peripheral retina. The topographic course of differentiation of the IPL generally corresponded to the course of maturation of ganglion and amacrine cells. Synaptogenesis and the expression of G‐protein–gated Kir3.2 channels accompanied the onset of stratification. These events coincide with the occurrence of robust and rhythmic spontaneous neuronal activity. The subsequent differentiation of the IPL seemed to be orchestrated by several mechanisms. J. Comp. Neurol. 460:1–12, 2003. © 2003 Wiley‐Liss, Inc.
Chemical anatomy of the human ventral striatum and adjacent basal forebrain structures
Authors: Prensa Lucía , Richard Sandra , Parent André 
Published: April 2003

AbstractCalbindin D‐28k (CB), calretinin (CR), substance P (SP), limbic system‐associated membrane protein (LAMP), choline acetyltransferase (ChAT), and acetylcholinesterase (AChE) were used as chemical markers to investigate the organization of the ventral striatum (VST) and adjacent structures in healthy human individuals. No clear boundary could be established between the dorsal striatum and the VST, and the core/shell subdivisions of nucleus accumbens (Acb) could be distinguished only at the midrostrocaudal level of the VST. The CB‐poor shell displayed intense immunostaining for SP and CR but only weak staining for LAMP. By contrast, the core was weakly stained for SP and CR and moderately stained for LAMP and CB. There was no difference between shell and core with regard to the cholinergic markers. The Acb harbored numerous ChAT‐ and CR‐immunoreactive cell bodies, the latter being distributed according to a marked, mediolaterally increasing gradient. The size of the ChAT‐ and CR‐immunoreactive perikarya in the Acb varied according to their location in the core and shell. The VST was surrounded by a chemically heterogeneous group of cell clusters referred to as interface islands. The CR‐rich caudal portion of the VST merged with the bed nucleus of the stria terminalis dorsally and the diagonal band of Broca ventromedially, the latter two structures displaying complex immunostaining patterns. The claustrum was markedly enriched in LAMP and harbored different types of CR‐ and CB‐immunopositive neurons. These results demonstrate that the neurochemical organization of the human VST is strikingly complex and exhibits a greater heterogeneity than the dorsal striatum. J. Comp. Neurol. 460:345–367, 2003. © 2003 Wiley‐Liss, Inc.
Differential distribution and developmental expression of synaptic vesicle protein 2 isoforms in the mouse retina
Authors: Wang Meng M. , Janz Roger , Belizaire Roger , Frishman Laura J. , Sherry David M. 
Published: April 2003

AbstractSynaptic vesicle protein 2 (SV2), a ubiquitous synaptic vesicle protein, is known to participate in the regulation of Ca2+‐mediated synaptic transmission, although its precise function has not been established. Three SV2 isoforms (SV2A, SV2B, SV2C) have been identified recently, each of which has a unique distribution in brain, suggesting synapse‐specific functions. To determine if SV2A, ‐B, and ‐C are differentially distributed among synapses in the retina and the sequence of their development, we examined their distribution and expression patterns immunocytochemically in adult and developing mouse retina. The three SV2 isoforms were differentially distributed in the synapses of the two plexiform layers in the adult retina. SV2A was present in cone, but not rod, terminals in the outer plexiform layer (OPL) and in many synaptic terminals in the inner plexiform layer (IPL). SV2B was present only in the ribbon synapse‐containing terminals of rod and cone photoreceptors and bipolar cells. SV2C was present in starburst amacrine cells, other conventional synapses in the IPL of unknown origin, and in presumptive interplexiform cell terminals in the INL and OPL. Each SV2 isoform was expressed in its distinct presynaptic terminals early and throughout postnatal development. In addition, SV2A was transiently expressed by developing horizontal cells. The unique distribution of each isoform suggests potentially distinct functions at different types of synapses, with SV2B having ribbon synapse‐specific functions, and SV2C being important for the functions of starburst amacrine cells. Rod and cone terminals contain different complements of SV2 isoforms, indicating that ribbon synapses are not all identical. The early expression of SV2 isoforms prior to initiation of synapse formation suggests that they may have important synapse‐specific roles during synaptogenesis. J. Comp. Neurol. 460:106–122, 2003. © 2003 Wiley‐Liss, Inc.
Anatomic organization of the ascending branch of the milk‐ejection reflex in sheep: Primary afferent neurons
Authors: Tsingotjidou Anastasia S. , Papadopoulos Georgios C. 
Published: April 2003

AbstractThe present study examines the anatomic characteristics of the primary afferent neurons that innervate the nipples and pseudonipples of ewes and the nipples of lambs. For this purpose, horseradish‐peroxidase coupled to wheat germ agglutinin (WGA‐HRP) was injected intradermally into the whole extent, the tip, or the base of the nipples and pseudonipples, as well as into a region of the posterior surface of the udder. After survival periods of 72–96 hours, dorsal root ganglia (DRG), segments of the spinal cord and medulla oblongata were sectioned and reacted histochemically with tetramethylbenzidine to reveal the transganglionically transported tracer. Injections of WGA‐HRP in the nipples and pseudonipples of the ewe resulted in labeled cells in the second to fifth ipsilateral lumbar spinal ganglia (L2–L5) and third and fourth (L3 and L4) lumbar spinal ganglia, respectively. Labeled cells after WGA‐HRP injections in the nipples of the lamb were found in the ipsilateral L3–L5 spinal ganglia. Central projections of the DRG‐labeled cells were found in the medial part of laminae I–III of the ipsilateral L3 and L4 spinal segments (ewe and lamb) and in the ipsilateral dorsal column nuclei (ewe). Central projections of the DRG‐labeled cells after injections in the pseudonipples of the ewe were located in the medial part of laminae I–III of the ipsilateral L3 spinal segment. The results of this study demonstrate that, whereas the innervation of the nipples of the ewe originates from four successive lumbar spinal ganglia (L2–L5), the innervation of the nipples of the lamb and the pseudonipples of the ewe originates from three (L3–L5) and two (L3 and L4) successive ganglia, respectively. J. Comp. Neurol. 460:66–79, 2003. © 2003 Wiley‐Liss, Inc.
Malformation of the radial glial scaffold in the dentate gyrus of reeler mice, scrambler mice, and ApoER2/VLDLR‐deficient mice
Authors: Weiss Karl Heinz , Johanssen Celine , Tielsch Albrecht , Herz Joachim , Deller Thomas , Frotscher Michael , Förster Eckart 
Published: April 2003

AbstractWe studied the postnatal development of the radial glial scaffold in the dentate gyrus of reeler mice, lacking the extracellular matrix protein Reelin, in scrambler mice, deficient in the intracellular adaptor protein disabled1 (Dab1), which is required for the transmission of the Reelin signal into the cell, and in mutant mice lacking the Reelin receptors apolipoprotein receptor 2 (ApoER2) and/or the very low density lipoprotein receptor (VLDLR), known to transmit the Reelin signal via Dab1. By immunolabeling for the glial fibrillary acidic protein (GFAP), we show that a regular dentate radial glial scaffold fails to form in mutants deficient of Reelin, Dab1, and VLDLR and ApoER2. Mutant mice lacking only one of the Reelin receptors, VLDLR or ApoER2, display a gradual expression of the radial glial defects seen in mutants that lack both receptors. Our results suggest that Reelin signaling via ApoER2, VLDLR, and Dab1 is required for the formation of a regular radial glial scaffold in the dentate gyrus. J. Comp. Neurol. 460:56–65, 2003. © 2003 Wiley‐Liss, Inc.