bluuebunny/crossref_metadata_2025_split huggingface dataset:
Anti–signal recognition particle autoantibody in patients with and patients without idiopathic inflammatory myopathy
Authors: Kao Amy H. , Lacomis David , Lucas Mary , Fertig Noreen , Oddis Chester V. 
Published: January 2004

AbstractObjectiveTo determine the long‐term outcome and associated clinical, serologic, and pathologic features in a cohort of patients with connective tissue disease (CTD) and the anti–signal recognition particle (anti‐SRP) autoantibody.MethodsSera and clinical data were collected prospectively from consecutive adult patients with polymyositis (PM; n = 134), dermatomyositis (n = 129), or other CTDs (predominantly systemic sclerosis [SSc; n = 790]). Patients were first evaluated during 1973–2001.ResultsNineteen patients with the anti‐SRP autoantibody were identified, 16 (84%) of whom had pure PM and 3 (2 with SSc and 1 with antisynthetase syndrome) had yet to develop features of myositis after a mean followup of 4.5 years (range 2.5–6 years). More SRP‐positive PM patients had severe proximal muscle weakness (50%) and muscle atrophy (67%) at initial presentation compared with antisynthetase‐positive PM controls. Cardiac involvement occurred in only 2 of 16 SRP‐positive PM patients (13%), and interstitial lung disease was noted in 3 of 13 SRP‐positive PM patients (23%) and in the 3 SRP‐positive nonmyositis patients. There was a relative lack of inflammation in muscle biopsy specimens from the SRP‐positive PM cohort. Other autoantibodies in the SRP‐positive patients included Ro/SSA (4 patients), Th/To (1 patient), and anti–PL‐12 (1 patient). Survival in the SRP‐positive PM patients was comparable with that seen in the cohort of SRP‐negative PM patients.ConclusionThe anti‐SRP autoantibody is not specific for PM. Severe muscle weakness and atrophy were prominent features in PM patients with anti‐SRP. Cardiac involvement was less common and survival was better in patients with anti‐SRP than has previously been reported.
Selective cleavage of nucleolar autoantigen B23 by granzyme B in differentiated vascular smooth muscle cells: Insights into the association of specific autoantibodies with distinct disease phenotypes
Authors: Ulanet Danielle B. , Flavahan Nicholas A. , Casciola‐Rosen Livia , Rosen Antony 
Published: January 2004

AbstractObjectiveTo investigate the association of specific autoantibodies with distinct disease phenotypes. The association of autoantibodies to nucleophosmin/B23 with pulmonary hypertension in scleroderma, and the susceptibility of autoantigens to cleavage by granzyme B (GB), provided a focus for these studies.MethodsIntact cells were subjected to cytotoxic lymphocyte granule–induced death, and the susceptibility of autoantigens to cleavage by GB was addressed by immunoblotting and/or by a novel immunofluorescence assay.ResultsB23 was cleaved efficiently by GB in vitro, but was highly resistant to cleavage by GB during cytotoxic lymphocyte granule–mediated death of many intact cell types. In contrast, this molecule was highly susceptible to GB‐mediated proteolysis exclusively in differentiated vascular smooth muscle cells. Topoisomerase I and several other GB substrates did not show this striking change in cleavage susceptibility in different cell types.ConclusionThese data demonstrate that the cleavage of B23 by GB in intact cells is dependent upon both cell type and phenotype. The susceptibility of this autoantigen (which is associated with a distinct pulmonary vascular phenotype in scleroderma) to GB‐mediated proteolysis selectively in vascular smooth muscle cells suggests that the GB‐cleavable conformation of autoantigens may occur selectively in the target tissue, and may play a role in shaping the phenotype‐specific autoimmune response.
Single and combined inhibition of tumor necrosis factor, interleukin‐1, and RANKL pathways in tumor necrosis factor–induced arthritis: Effects on synovial inflammation, bone erosion, and cartilage destruction
Authors: Zwerina Jochen , Hayer Silvia , Tohidast‐Akrad Makiyeh , Bergmeister Helga , Redlich Kurt , Feige Ulrich , Dunstan Colin , Kollias Giorgos , Steiner Günter , Smolen Josef , Schett Georg 
Published: January 2004

AbstractObjectiveTo investigate the efficacy of single and combined blockade of tumor necrosis factor (TNF), interleukin‐1 (IL‐1), and RANKL pathways on synovial inflammation, bone erosion, and cartilage destruction in a TNF‐driven arthritis model.MethodsHuman TNF–transgenic (hTNFtg) mice were treated with anti‐TNF (infliximab), IL‐1 receptor antagonist (IL‐1Ra; anakinra), or osteoprotegerin (OPG; an OPG‐Fc fusion protein), either alone or in combinations of 2 agents or all 3 agents. Synovial inflammation, bone erosion, and cartilage damage were evaluated histologically.ResultsSynovial inflammation was inhibited by anti‐TNF (−51%), but not by IL‐1Ra or OPG monotherapy. The combination of anti‐TNF with either IL‐1Ra (−91%) or OPG (−81%) was additive and almost completely blocked inflammation. Bone erosion was effectively blocked by anti‐TNF (−79%) and OPG (−60%), but not by IL‐1Ra monotherapy. The combination of anti‐TNF with IL‐1Ra, however, completely blocked bone erosion (−98%). Inhibition of bone erosion was accompanied by a reduction of osteoclast numbers in synovial tissue. Cartilage destruction was inhibited by anti‐TNF (−43%) and was weakly, but not significantly, inhibited by IL‐1Ra, but was not inhibited by OPG monotherapy. The combination of anti‐TNF with IL‐1Ra was the most effective double combination therapy in preventing cartilage destruction (−80%). In all analyses, the triple combination of anti‐TNF, IL‐1Ra, and OPG was not superior to the double combination of anti‐TNF and IL‐1Ra.ConclusionArticular changes caused by chronic overexpression of TNF are not completely blockable by monotherapies that target TNF, IL‐1, or RANKL. However, combined approaches, especially the combined blockade of TNF and IL‐1 and, to a lesser extent, TNF and RANKL, lead to almost complete remission of disease. Differences in abilities to block synovial inflammation, bone erosion, and cartilage destruction further strengthen the rationale for using combined blockade of more than one proinflammatory pathway.
Oligodeoxynucleotides containing CpG motifs can induce T cell–dependent arthritis in rats
Authors: Svelander Lena , Erlandsson Harris Helena , Lorentzen Johnny C. , Trollmo Christina , Klareskog Lars , Bucht Anders 
Published: January 2004

AbstractObjectiveTo investigate whether CpG oligodeoxynucleotides (ODNs) can induce or accelerate arthritis in rats.MethodsThe CpG‐induced response was studied by recording joint inflammation, cell activation in draining lymph nodes, and levels of the acute‐phase reactant α1‐acid glycoprotein (AGP) in sera. The role of T cells was investigated by in vivo administration of monoclonal antibodies specific for the T cell receptor α/β (TCRα/β), followed by analysis of cell phenotypes by flow cytometry.ResultsOne intradermal injection of CpG ODN emulsified with Freund's incomplete adjuvant (IFA) induced arthritis in LEW and LEW.1AV1 rats, while the control ODN sequence without CpG motifs or IFA alone did not trigger disease. The CpG/IFA and control‐ODN/IFA injections induced lymphoplasia as well as elevated levels of interleukin‐1β and interferon‐γ messenger RNA in lymph nodes. The arthritis was preceded by elevated levels of AGP in serum. In vivo administration of anti‐TCRα/β antibodies after disease induction caused decreased expression of the TCR–CD3 complex on circulating T cells and ameliorated the arthritis.ConclusionWe demonstrated that injection with immunostimulatory CpG, both in phosphorothioate‐modified and native forms, can induce a T cell–dependent joint‐specific inflammation in LEW and LEW.1AV1 rat strains. This arthritis is preceded by signs of activation of the innate immune system. Since unmethylated CG dinucleotides are common in bacterial DNA but rare in mammalian DNA, our results indicate that exposure to bacterial DNA during infection may contribute to arthritis induction by amplifying the innate immune response.
Neural stem and progenitor cells in nestin‐GFP transgenic mice
Authors: Mignone John L. , Kukekov Valery , Chiang Ann‐Shyn , Steindler Dennis , Enikolopov Grigori 
Published: January 2004

AbstractNeural stem cells generate a wide spectrum of cell types in developing and adult nervous systems. These cells are marked by expression of the intermediate filament nestin. We used the regulatory elements of the nestin gene to generate transgenic mice in which neural stem cells of the embryonic and adult brain are marked by the expression of green fluorescent protein (GFP). We used these animals as a reporter line for studying neural stem and progenitor cells in the developing and adult nervous systems. In these nestin‐GFP animals, we found that GFP‐positive cells reflect the distribution of nestin‐positive cells and accurately mark the neurogenic areas of the adult brain. Nestin‐GFP cells can be isolated with high purity by using fluorescent‐activated cell sorting and can generate multipotential neurospheres. In the adult brain, nestin‐GFP cells are ∼1,400‐fold more efficient in generating neurospheres than are GFP‐negative cells and, despite their small number, give rise to 70 times more neurospheres than does the GFP‐negative population. We characterized the expression of a panel of differentiation markers in GFP‐positive cells in the nestin‐GFP transgenics and found that these cells can be divided into two groups based on the strength of their GFP signal: GFP‐bright cells express glial fibrillary acidic protein (GFAP) but not βIII‐tubulin, whereas GFP‐dim cells express βIII‐tubulin but not GFAP. These two classes of cells represent distinct classes of neuronal precursors in the adult mammalian brain, and may reflect different stages of neuronal differentiation. We also found unusual features of nestin‐GFP–positive cells in the subgranular cell layer of the dentate gyrus. Together, our results indicate that GFP‐positive cells in our transgenic animals accurately represent neural stem and progenitor cells and suggest that these nestin‐GFP–expressing cells encompass the majority of the neural stem cells in the adult brain. J. Comp. Neurol. 469:311–324, 2004. © 2004 Wiley‐Liss, Inc.
Neurogenesis and stereological morphometry of calretinin‐immunoreactive GABAergic interneurons of the neostriatum
Authors: Rymar Vladimir V. , Sasseville Rachel , Luk Kelvin C. , Sadikot Abbas F. 
Published: January 2004

AbstractWe determined the neurogenesis characteristics of a distinct subclass of rat striatum γ‐aminobutyric acidergic (GABAergic) interneurons expressing the calcium‐binding protein calretinin (CR). Timed‐pregnant rats were given an intraperitoneal injection of 5‐bromo‐2′‐deoxyuridine (BrdU), a marker of cell proliferation, on designated days between embryonic day 12 (E12) and E21. CR‐immunoreactive (‐IR) neurons and BrdU‐positive nuclei were labeled in the adult neostriatum by double immunohistochemistry, and the proportion of double‐labeled cells was quantified. CR‐IR interneurons of the neostriatum show maximum birth rates (>10% double labeling) between E14 and E17, with a peak at E15. CR‐IR interneurons occupying the lateral half of the neostriatum become postmitotic prior to medial neurons. In the precomissural neostriatum, the earliest‐born neurons occupy the lateral quadrants and the latest‐born neurons occupy the dorsomedial sector. No significant rostrocaudal neurogenesis gradient is observed. CR‐IR neurons make up 0.5% of the striatal population and are localized in both the patch and the matrix compartments. CR‐IR neurons of the patch compartment are born early (E13–15), with later‐born neurons (E16–18) populating mainly the matrix compartment. CR‐IR cells of the neostriatum are a distinct subclass of interneurons that are born at an intermediate time during striatal development and share common neurogenesis characteristics with other interneurons and projection neurons produced in the ventral telencephalon. J. Comp. Neurol. 469:325–339, 2004. © 2004 Wiley‐Liss, Inc.
Morphologic analysis and classification of ganglion cells of the chick retina by intracellular injection of lucifer yellow and retrograde labeling with DiI
Authors: Naito Jumpei , Chen Yaoxing 
Published: January 2004

AbstractRetinal ganglion cells (RGCs) of chicks were labeled by using the techniques of intracellular filling with Lucifer Yellow and retrograde axonal labeling with carbocyanine dye (DiI). Labeled RGCs were morphologically analyzed and classified into four major groups: Group I cells (57.1%) with a small somal area (77.5 μm2 on average) and narrow dendritic field (17,160 μm2 on average), Group II cells (28%) with a middle‐sized somal area (186 μm2) and middle‐sized dendritic field (48,800 μm2), Group III cells (9.9%) with a middle‐sized somal area (203 μm2) and wide dendritic field (114,000 μm2), and Group IV cells (5%) with a large somal area (399 μm2) and wide dendritic field (117,000 μm2). Of the four groups, Groups I and II were further subdivided into two types, simple and complex, on the basis of dendritic arborization: Groups Is, Ic, and Groups IIs, IIc. However, Group III and IV showed either a simple or complex type, Group IIIs and Group IVc, respectively. The density of branching points of dendrites was approximately 10 times higher in the complex types (18,350, 6,190, and 3,520 points/mm2 in Group Ic, IIc, and IVc, respectively) than in the simple types (1,890, 640, and 480 points/mm2 in Group Is, IIs, and IIIs). The branching density of Group I cells was extremely high in the central zone. The chick inner plexiform layer was divided into eight sublayers by dendritic strata of RGCs and 26 stratification patterns were discriminated. The central and peripheral retinal zones were characterized by branching density of dendrites and composition of RGC groups, respectively. J. Comp. Neurol. 469:360–376, 2004. © 2004 Wiley‐Liss, Inc.
Cellular correlates of progressive hearing loss in 129S6/SvEv mice
Authors: Ohlemiller Kevin K. , Gagnon Patricia M. 
Published: January 2004

AbstractSeveral strains of mice hear well initially but show progressive sensorineural hearing loss. Affected cochlear cell types include all those known to be affected in human age‐related hearing loss (ARHL), or presbycusis. Thus these mice have been offered as models of human ARHL. At present, however, few mouse ARHL models are sufficiently well described to serve as the basis for specific hypotheses about human ARHL. We examined 1‐month‐old and 15‐month‐old 129S6/SvEv (129S6) mice and compared them with BALB/cJ and CBA/J mice. Age‐related elevation of compound action potential thresholds was interpreted in the light of endocochlear potentials and changes in hair cells, afferent neurons, fibrocytes in spiral limbus and ligament, and supporting cells within the organ of Corti. Aging in 129S6 mice was associated with high‐frequency hearing loss. Four components of age‐related cochlear degeneration emerged from quantitative analyses, including 1) basal loss of outer hair cells; 2) basal loss of type IV fibrocytes in the spiral ligament; 3) apical loss of fibrocytes in spiral limbus, and 4) anomalies of supporting cells in the cochlear base. Although neuronal loss was not consistently found, two mice showed loss of afferent dendrites and cell bodies in the cochlear apex without inner hair cell loss. Despite multifaceted degeneration, hearing loss in 129S6 mice appears to be best explained by degenerative changes in outer hair cells and in the organ of Corti, conforming to human sensory ARHL. Age‐related changes in the apical spiral limbus may promote pathology of the medial organ of Corti and eventual loss of afferent neurons, with possible implications for human neural ARHL. J. Comp. Neurol. 469:377–390, 2004. © 2004 Wiley‐Liss, Inc.
Efferent connections of septal nuclei of the domestic chick (Gallus domesticus): An anterograde pathway tracing study with a bearing on functional circuits
Authors: Montagnese Catherine M. , Székely Andrea D. , Ádám Ágota , Csillag András 
Published: January 2004

AbstractSmall iontophoretic injections of the anterograde tracerPhaseolus vulgarisleucoagglutinin were placed in different subregions of the septum of domestic chicks. The main targets of septal projections comprised the ipsi‐ and contralateral septal nuclei, including the nucleus of the diagonal band, basal ganglia, including the ventral paleostriatum, lobus parolfactorius, nucleus accumbens, and olfactory tubercle, archistriatum, piriform cortex, and anterior neostriatum. Further diencephalic and mesencephalic septal projections were observed in the ipsilateral preoptic region, hypothalamus (the main regions of afferentation comprising the lateral hypothalamic nuclei, ventromedial, paraventricular and periventricular nuclei, and the mammillary region), dorsal thalamus, medial habenular and subhabenular nuclei, midbrain central gray, and ventral tegmental area. Contralateral projections were also encountered in the septal nuclei, ventral paleostriatum, periventricular and anteromedial hypothalamic nuclei, suprachiasmatic nucleus, and the lateral hypothalamic area. Avian septal efferents are largely similar to those of mammals, the main differences being a relatively modest hippocampal projection arising mainly from the nucleus of the diagonal band (as confirmed by a specific experiment with the retrograde pathway tracer True blue), the lack of interpeduncular projection, and a greater contingent of amygdalar efferents arising from the lateral septum rather than the nucleus of the diagonal band. This pattern of connectivity is likely to reflect an important role of the avian septal nuclei in the coordination of limbic circuits and the integration of a wide variety of information sources modulating the appropriate behavioral responses: attention and arousal level, memory formation, hormonally mediated behaviors, and their affective components (such as ingestive, reproductive, and parental behaviors), social interaction, locomotor modulation, and circadian rhythm. J. Comp. Neurol. 469:437–456, 2004. © 2004 Wiley‐Liss, Inc.
Inner retinal abnormalities in a mouse model of Leber's congenital amaurosis
Authors: Pignatelli Vincenzo , Cepko Constance Louise , Strettoi Enrica 
Published: January 2004

AbstractLeber's congenital amaurosis (LCA) is the earliest and most severe form in the world of genetic retinal dystrophy causing blindness. An animal model of LCA was recently created in which the cone‐rod homeobox (crx) gene was disrupted using homologous recombination. Crx−/− mice display abnormal development of photoreceptors followed by their degeneration. We analyzed the morphology of inner retinal cells in crx−/− mice in order to evaluate the effects of abnormal photoreceptor development and death upon other retinal neurons. The identification of a time window during which inner retinal cells are still viable could be very important in view of the possibilities that photoreceptor transplantation or gene therapy might be used to restore vision in LCA. We used a combination of immunocytochemical and confocal microscopy techniques to screen the crx−/− inner retina and verify its morphological integrity after photoreceptor degeneration. We found significant morphological alterations in second‐order neurons in crx−/− animals. The appearance of mutant retinas after photoreceptor death is indistinguishable from that of the retinal degeneration (rd/rd) mouse, a different genetic model of a retinal disease characterized by photoreceptor degeneration. However, at early stages of photoreceptor degeneration the morphology of retinal cells in the crx−/− mutant is considerably well preserved. It is likely that different genetic mechanisms that cause abnormal photoreceptor development and/or degeneration lead to a common pathway that determines second‐order neuron modifications. The severity of modifications is linked to the timing of onset of the degeneration and appears to increase with time. J. Comp. Neurol. 469:351–359, 2004. © 2004 Wiley‐Liss, Inc.
Development of vimentin and glial fibrillary acidic protein immunoreactivities in the brain of gray mullet (Chelon labrosus), an advanced teleost
Authors: Arochena Mercedes , Anadón Ramón , Díaz‐Regueira Sofía M. 
Published: January 2004

AbstractPrevious studies in teleosts have revealed the presence of the intermediate filaments vimentin (Vim) and glial fibrillary acidic protein (GFAP) in glial cells of the spinal cord and/or some brain regions, but there is no comprehensive study of their distribution and developmental changes in fishes. Here, the distribution of Vim and GFAP immunoreactivities was studied in the brain of larvae, juveniles, and adults of an advanced teleost, the gray mullet (Chelon labrosus). A different sequence of appearance was observed for expression of these proteins: Vim levels decreased with age, whereas GFAP increased. In general, both immunoreactivities were expressed early in perikarya and endfeet of ependymocytes (tanycytes), whereas expression in radial processes appeared later. In large larvae, the similar expression patterns of Vim and GFAP suggest that some of these glial cells contain both proteins. Subependymal radial glia cells were observed mainly in the optic tectum, exhibiting Vim and GFAP immunoreactivity. The only immunoreactive cells with astrocyte‐like morphology were observed in the optic chiasm of the adult, and they were positive for both GFAP and Vim. The perivascular processes of glial cells showed a different distribution of Vim and GFAP during development and had a caudorostral sequence of appearance of immunoreactivities similar to that observed for ependymal and radial glia cells. Several circumventricular organs (the organon vasculosum hypothalami, saccus vasculosus, and area postrema) exhibited highly specialized Vim‐ and/or GFAP‐expressing glial cells. The glial cells of the midline septa of several brain regions were also Vim and/or GFAP immunoreactive. In the adult brain, tanycytes retain Vim expression in several brain regions. As in other vertebrates, the regions with Vim‐immunoreactive ventricular and midline glia may represent areas with the capability of plasticity and regeneration in adult brain. J. Comp. Neurol. 469:413–436, 2004. © 2004 Wiley‐Liss, Inc.