bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of PINCH in Schwann cells and DRG neurons: Shuttling and signaling after nerve injury
Authors: Campana W. Marie , Myers Robert R. , Rearden Ann 
Published: January 2003

AbstractParticularly interesting new cysteine‐histidine rich protein (PINCH) is a double zinc finger domain (LIM)‐only adapter protein that functions to recruit the integrin‐linked kinase (ILK) to sites of integrin activation. Genetic studies have shown that PINCH and ILK are required for integrin signaling. Since integrin activation is associated with Schwann cell migration, neurite outgrowth and regeneration, this study examined PINCH in the normal peripheral nervous system and after chronic constriction injury (CCI) in adult Sprague‐Dawley rats. Immunohistochemistry identified PINCH immunoreactivity in cell bodies of dorsal root ganglia (DRG) neurons, axons, satellite cells, and Schwann cells. PINCH immunostaining was localized to the membrane of uninjured DRG cell bodies consistent with its localization at a site of integrin activation. In contrast, 5 days following CCI, PINCH immunostaining was diffuse throughout the DRG cell cytoplasm. Confocal microscopy of primary and transformed Schwann cells localized PINCH in cytoplasmic, perinuclear and nuclear areas. Examination of the PINCH sequence revealed a putative leucine‐rich nuclear export signal (NES) and an overlapping basic nuclear localization signal (NLS). To demonstrate nuclear export of PINCH, rabbit anti‐PINCH IgG was microinjected into Schwann cell nuclei and allowed to combine with PINCH contained within the nucleus. Immunofluorescence showed that the PINCH and anti‐PINCH IgG complex rapidly translocated to the cytoplasm. Treatment with leptomycin B caused nuclear accumulation of PINCH, indicating that the CRM1 pathway mediates nuclear export of PINCH. ILK activity in Schwann cells was enhanced by platelet‐derived growth factor (PDGF) and tumor necrosis factor α. PINCH immunoprecipitates from PDGF‐ and TNFα‐stimulated Schwann cells contained several high‐molecular‐weight threonine‐phosphorylated proteins. Taken together, these results indicate that PINCH is an abundant shuttling/signaling protein in Schwann cells and DRG neurons. GLIA 41:213–223, 2003. © 2003 Wiley‐Liss, Inc.
Olfactory ensheathing cells of the lamina propria in vivo and in vitro
Authors: Au Edmund , Roskams A. Jane 
Published: January 2003

AbstractOlfactory ensheathing cells (OECs) continuously support the regeneration of olfactory receptor neurons (ORNs). In addition, OECs promote regeneration of neurons within the CNS in a number of transplantation paradigms, but details of exactly how they support regeneration remain elusive. The majority of studies using OECs to promote regeneration have thus far focused on understanding the cell biology of OECs purified from the olfactory bulb (OB). Here we show that a population of OECs similar to those obtained from the OB is present in the lamina propria (LP) beneath the olfactory epithelium (OE). These OECs are the first glial cells encountered by the axons of developing ORNs as they exit the OE and display distinct and variable expression of p75, S100β, GFAP, and O4, characteristic markers of bulb OECs. Once purified in vitro, they display Schwann cell‐like and astrocyte‐like properties and expand rapidly. In addition to resembling OB‐OECs, LP‐OECs also express a unique combination of developmentally important proteins—CD 44, β1 integrin, P200, Notch 3, NG2, VEGF, and PACAP and CREB binding protein (CBP/p300)—not previously reported in OB‐OECs. These data suggest that LP‐OECs, like OB‐OECs, are a developmentally distinct class of glia that are capable of both immature and mature function, depending on environmental stimuli, within the adult nervous system. GLIA 41:224–236, 2003. © 2003 Wiley‐Liss, Inc.
Nodal sodium channel domain integrity depends on the conformation of the paranodal junction, not on the presence of transverse bands
Authors: Rosenbluth Jack , Dupree Jeffrey L. , Popko Brian 
Published: January 2003

AbstractOur understanding of the role that axoglial interactions play in node of Ranvier formation and maintenance remains incomplete. Previous studies of CNS myelinated fibers of CGT‐null mice showed abnormalities in the arrangement of paranodal myelin loops and absence of a conspicuous component of the paranodal junction, the ridge‐like intercellular transverse bands. Axolemmal sodium channel domains were largely preserved at nodes of Ranvier but displayed some abnormalities in form. Using a combination of freeze‐fracture and immunocytochemical methods, we have found additional evidence documenting abnormalities in the size, shape, and location of axolemmal sodium channel clusters in CGT‐null mice as well as evidence that these nodal abnormalities are complementary to the organization of paranodal myelin loops, despite the absence of transverse bands. We conclude that the differentiated form of the nodal axolemma and the distribution of axolemmal sodium channels depend on the conformation of paranodal axoglial contacts but not on the presence of transverse bands at the sites of contact. GLIA 41:318–325, 2003. © 2003 Wiley‐Liss, Inc.
Upregulation of gp130 and STAT3 activation in the rat hippocampus following transient forebrain ischemia
Authors: Choi Jeong‐Sun , Kim Seong Yun , Cha Jung‐Ho , Choi Yun‐Sik , Sung Ki‐Wug , Oh Seong Taek , Kim Ok Nyu , Chung Jin‐Woong , Chun Myung‐Hoon , Lee Sang Bok , Lee Mun‐Yong 
Published: January 2003

AbstractTo determine whether the pathophysiological processes after transient forebrain ischemia are mediated via a signal pathway involving gp130 (a signal transducer for the interleukin‐6 family), we analyzed changes in the expression of gp130 and its downstream transcription factor, signal transducer and activator of transcription factor 3 (STAT3), in the rat hippocampus of a four‐vessel occlusive ischemia model. Expression of gp130 mRNA was restricted to neurons of the pyramidal cell and granule cell layers in control animals. Four hours after ischemic injury, astrocytes expressed gp130 mRNA. Expression of gp130 increased preferentially in the CA1 and dentate hilar regions, and was maintained for at least 2 weeks. Increase in gp130 expression was accompanied by the activation of STAT3 following ischemic injury. Four hours after injury, STAT3 and phosphorylated STAT3 (pSTAT3) were observed in the nuclei of the dentate hilar region, and sequentially in the CA1 region at day 1. By day 3, STAT3 immunoreactivity markedly increased in these areas, where small cells with the morphology of astrocytes showed nuclear and cytoplasmic STAT3 and nuclear pSTAT3 immunoreactivities. These patterns were especially maintained in the CA1 area until 14 days of reperfusion. Double‐labeling experiments revealed that the cells expressing STAT3 and pSTAT3 were glial fibrillary acidic protein‐expressing reactive astrocytes. These results show a coordinated and long‐lasting upregulation of gp130 mRNA and STAT3 activation in reactive astrocytes of the postischemic hippocampus, indicating that they may be involved in the astrocytic response to an ischemic insult. GLIA 41:237–246, 2003. © 2003 Wiley‐Liss, Inc.
Highly differential expression of SN1, a bidirectional glutamine transporter, in astroglia and endothelium in the developing rat brain
Authors: Boulland Jean‐Luc , Rafiki Amina , Levy Line M. , Storm‐Mathisen Jon , Chaudhry Farrukh A. 
Published: January 2003

AbstractThe transmitters glutamate and GABA also subserve trophic action and are required for normal development of the brain. They are formed from glutamine, which may be synthesized in glia or extracted from the blood. In the adult, the glutamine transporter SN1 is expressed in the astroglia. SN1 works in both directions, depending on the concentration gradients of its substrates and cotransported ions, and is thought to regulate extracellular glutamine and to supply the neurons with the transmitter precursor. In this article, we have quantified the expression and studied the localization of SN1 at different developmental stages. SN1 is expressed in astroglia throughout the CNS from embryonic stages through adulthood. No indication of SN1 staining in neuronal elements has been obtained at any stage. Quantitative immunoblotting of whole brain extracts demonstrates increasing expression of SN1 from P0, reaching a peak at P14, twice the adult level. A moderate and slower rise and fall of the expression levels of SN1 occurs in the cerebellum. Strong transient SN1‐like staining is also found in Bergmann glia and vascular endothelium in the first postnatal weeks. Strong intracellular staining in the same time period suggests a high rate of SN1 synthesis in the early postnatal period. This coincides with the increasing levels of glutamate and GABA in the CNS and with the time course of synaptogenesis. This study suggests that the expression of SN1 is highly regulated, correlating with the demand for glutamine during the critical period of development. GLIA 41:260–275, 2003. © 2003 Wiley‐Liss, Inc.
Recovery from lactacidosis‐induced glial cell swelling with the aid of exogenous anion channels
Authors: Nabekura Takashi , Morishima Shigeru , Cover Timothy L. , Mori Shin‐Ichiro , Kannan Hiroshi , Komune Shizuo , Okada Yasunobu 
Published: January 2003

AbstractHypotonic challenge induces transient swelling in glial cells, which is typically followed by a regulatory volume decrease (RVD). In contrast, lactic acidosis (lactacidosis) induces persistent cell swelling in astrocytes without an accompanying RVD. In the present study, we studied the mechanisms by which lactacidosis interferes with normal volume regulation in rat astrocytic glioma C6 cells. Following exposure of C6 cells to a hypotonic challenge, a current was detected that exhibited properties consistent with those of volume‐sensitive outwardly rectifying (VSOR) anion channels. When exposed to in vitro conditions designed to simulate lactacidosis, C6 cells failed to respond to hypotonic stress with an RVD, and VSOR anion currents were not activated. When added to C6 cells, an anion channel‐forming protein purified from Helicobacter pylori, VacA, was found to form anion‐selective channels in the plasma membrane, and the activity of the VacA channel was not affected by lactacidosis (pH 6.2). Cells preincubated with VacA and then exposed to lactacidotic conditions underwent transient swelling followed by RVD. In contrast, application of a cation ionophore, gramicidin, failed to inhibit lactacidosis‐induced persistent cell swelling. From these results, we conclude that inhibition of a volume‐sensitive anion channel contributes to persistent swelling induced by lactacidosis in glial cells. Introduction of anion channel activity into glial cells might provide a novel approach for treating cerebral edema, which is associated with lactacidosis in cerebral ischemia or head injury. GLIA 41:247–259, 2003. © 2003 Wiley‐Liss, Inc.
Oligodendrocyte precursor hypercellularity and abnormal retina development in mice overexpressing PDGF‐B in myelinating tracts
Authors: Forsberg‐Nilsson Karin , Erlandsson Anna , Zhang Xiao‐Qun , Ueda Hideho , Svensson Kristian , Nistér Monica , Trapp Bruce D. , Peterson Alan C. , Westermark Bengt 
Published: January 2003

AbstractPlatelet‐derived growth factor (PDGF) influences the generation of neurons and glia during embryogenesis and in early postnatal life. In an attempt to determine the consequences of an overexpression of PDGF‐B during the first weeks of life, we targeted transgenic expression of a human PDGF‐B cDNA to myelinating tracts using the promoter region of the myelin basic protein (MBP) gene. Transgenic mRNA and protein were expressed in the brain and the expression profile of the human PDGF‐B during early postnatal development closely paralleled that of the endogenous mouse MBP gene. The gross morphological appearance of transgenic brains was normal but at the cellular level several phenotypic alterations could be identified. In white matter tracts such as the corpus callosum and cerebellar medulla, there was a marked hypercellularity. The number of oligodendrocyte precursors was increased and astrocytes were more abundant. In adult mice carrying the MBP–PDGF‐B transgene, however, myelination appeared normal and the amount of oligodendrocytes was similar to that of control littermates. In addition to the phenotypic alterations in the brain, investigation of eye structure revealed a striking disorganization of retinal architecture. The retina was folded with cells collected in papillar or follicular‐like structures. Retinal whole mount preparations after India ink perfusion revealed capillary disorganization with large‐caliber vessels supporting only a few fine branches. Our observations strengthen the notion that PDGF is an important effector molecule in postnatal CNS development. GLIA 41:276–289, 2003. © 2003 Wiley‐Liss, Inc.
Expression of protein zero is increased in lesioned axon pathways in the central nervous system of adult zebrafish
Authors: Schweitzer Jörn , Becker Thomas , Becker Catherina G. , Schachner Melitta 
Published: January 2003

AbstractThe immunoglobulin superfamily molecule protein zero (P0) is important for myelin formation and may also play a role in adult axon regeneration, since it promotes neurite outgrowth in vitro. Moreover, it is expressed in the regenerating central nervous system (CNS) of fish, but not in the nonregenerating CNS of mammals. We identified a P0 homolog in zebrafish. Cell type‐specific expression of P0 begins in the ventromedial hindbrain and the optic chiasm at 3–5 days of development. Later (at 4 weeks) expression has spread throughout the optic system and spinal cord. This is consistent with a role for P0 in CNS myelination during development. In the adult CNS, glial cells constitutively express P0 mRNA. After an optic nerve crush, expression is increased within 2 days in the entire optic pathway. Expression peaks at 1 to 2 months and remains elevated for at least 6 months postlesion. After enucleation, P0 mRNA expression is also upregulated but fails to reach the high levels observed in crush‐lesioned animals at 4 weeks postlesion. Spinal cord transection leads to increased expression of P0 mRNA in the spinal cord caudal to the lesion site. The glial upregulation of P0 mRNA expression after a lesion of the adult zebrafish CNS suggests roles for P0 in promoting axon regeneration and remyelination after injury. GLIA 41:301–317, 2003. © 2003 Wiley‐Liss, Inc.
Astrocytes are the major intracerebral source of macrophage inflammatory protein‐3α/CCL20 in relapsing experimental autoimmune encephalomyelitis and in vitro
Authors: Ambrosini Elena , Columba‐Cabezas Sandra , Serafini Barbara , Muscella Antonella , Aloisi Francesca 
Published: January 2003

AbstractMacrophage inflammatory protein‐3α/CCL20 is a recently identified chemokine that binds to CCR6 and acts as a chemoattractant for memory/differentiated T‐cells, B‐cells, and immature dendritic cells. We have previously reported that CCL20 and CCR6 mRNAs are expressed in the CNS of SJL mice with experimental autoimmune encephalomyelitis (EAE) and that CCL20 is produced by CNS‐infiltrating leukocytes at disease onset and, additionally, by intraparenchymal astrocyte‐like cells during disease relapses. In this study, we provide further immunohistochemical evidence that astrocytes represent the main CNS source of CCL20 during EAE. Moreover, we show that the proinflammatory cytokines interleukin‐1β and tumor necrosis factor‐α, but not interferon‐γ, induce expression of CCL20 mRNA and secretion of CCL20 protein in cultures of mouse brain‐derived astrocytes. We also show that supernatants from cytokine‐activated astrocytes stimulate the migration of polarized T helper cells and that this effect is partially inhibited by anti‐CCL20 antibody. These findings suggest that, through secretion of CCL20, astrocytes could play an important role in orchestrating the recruitment of specific leukocyte subsets to the inflamed CNS and in regulating CNS‐targeted immune responses. GLIA 41:290–300, 2003. © 2003 Wiley‐Liss, Inc.
Synthesis of high specific activity 35S‐labelled N‐methanesulfonyl farnesylcysteine and a photoactive analog
Authors: Kale Tamara A. , Raab Conrad , Yu Nathan , Aquino Evelyn , Dean Dennis C. , Distefano Mark D. 
Published: January 2003

AbstractPrenylated cysteine analogs, which mimic the prenylated cysteine residue of prenylated GTP‐binding proteins (G‐proteins), have been used in a variety of contexts for the study of prenylated G‐protein behavior. In earlier work in this area, we prepared the photoactive analog [35S]4 and showed that it labelled RhoGDI upon photolysis; those results were consistent with the idea that GDI contains an isoprenoid binding site. Here, we describe the preparation of [35S]N‐methanesulfonyl labelled analogs (1a and 2a) of N‐acetyl farnesylcysteine and its methyl ester together with an improved synthetic procedure for photoactive analogs 3 and 4; specific activities of ∼1100 Ci/mmol were achieved. Compounds 1a and 2a in unlabelled form were used as competitors in photolysis reactions to show that the methanesulfonamido group is a reasonable acetamide substitution. Additional experiments show that the photoactive ester [35S]3 can cross‐link GDI in both purified form and crude bacterial extract. However, the extent of cross‐linking obtained with the ester ([35S]3) is significantly less than that observed with the free acid ([35S]4) despite the fact that the esterified form probably more closely reflects the structure of the C‐terminus of a prenylated protein; using the GDI·Cdc42 co‐crystal structure, the structural basis for these results is discussed. Copyright © 2002 John Wiley & Sons, Ltd.
Preparation of 4‐[11C]methylmetaraminol, a potential PET tracer for assessment of myocardial sympathetic innervation
Authors: Langer Oliver , Forngren Tobias , Sandell Johan , Dollé Frédéric , Långström Bengt , Någren Kjell , Halldin Christer 
Published: January 2003

AbstractThe false adrenergic neurotransmitter [11C]meta‐hydroxyephedrine ([11C]HED) is currently the PET tracer of choice for assessment of myocardial sympathetic innervation. The molecule is metabolised in the 4‐position of the aromatic ring. The resulting radiolabelled metabolites need to be measured in order to obtain an arterial input function. Our aim was the development of a PET tracer with an increased metabolic stability relative to [11C]HED. We selected 4‐methylmetaraminol as a candidate molecule for radiolabelling with 11C (t1/2 20.4 min). Our radiosynthetic approach towards 4‐[11C]methylmetaraminol involved a palladium‐catalyzed cross‐coupling reaction of a protected 4‐trimethylstannyl derivative of metaraminol with [11C]methyl iodide followed by removal of the protective groups. 4‐[11C]methylmetaraminol was obtained in a final decay‐corrected radiochemical yield of 20–25% within a synthesis time of 60–80 min. The specific radioactivity at the end of the synthesis ranged from 18–37 to GBq/μmol. The unlabelled reference molecule, 4‐methylmetaraminol, was prepared in a 5‐step synthesis starting from metaraminol. A biological evaluation of 4‐[11C]methylmetaraminol is in progress and the results will be reported elsewhere. Copyright © 2002 John Wiley & Sons, Ltd.
Synthesis and characterization of the potent cannabinoid agonist [naphthyl‐3H] WIN 55212‐2 at high specific activity
Authors: Seguin Richard J. , Filer Crist N. 
Published: January 2003

Abstract[Naphthyl‐3H] WIN 55212‐2 was prepared at high specific activity by the catalytic tritiation of dibromo precursor 3. Product 4 was characterized by chromatography as well as tritium NMR and proven to be a useful radioligand. Copyright © 2002 John Wiley & Sons, Ltd.
Synthesis and biological characteristics of the Technetium‐99m triamide derivatives of mercaptoacetyltriglycine (MAG3)
Authors: Okarvi S. M. , Adriaens P. , Verbruggen A. M. 
Published: January 2003

AbstractA number of MAG3‐derivatives, containing the three‐amide functions modified by inverting the sequence –CO–NH– to –NH–CO– in the first‐ and/or second‐amide functions, have been labelled with 99mTc in order to study the renal characteristics of the resulting MAG3‐derivatives versus the reference 99mTc‐MAG3. The 99mTc‐MAG3‐derivatives displayed HPLC‐profiles similar to that of 99mTc‐MAG3. Furthermore, in mice they exhibited biological behaviour comparable or even superior to 99mTc‐MAG3, which indicates that the sequence of the first‐ and/or second‐amide bond in 99mTc‐MAG3 affects the biological behaviour only to a limited degree. However, in baboon the plasma clearance of the 99mTc‐MAG3‐derivatives was relatively slower than 99mTc‐MAG3, which underlines the inter‐species variability. Copyright © 2002 John Wiley & Sons, Ltd.
Synthesis of PNU‐243922 labelled with 14C
Authors: Felicini C. , Fontana E. , Giribone D. , M. Nilsson B. , Österlund K. , Paptchikhine A. 
Published: January 2003

AbstractThe arylpiperazine PNU‐243922 (1) has been labelled with 14C. A two‐step sequence starting from the 14C labelled alcohol 6a led to radiochemically pure (>98%) [14C]PNU‐243922 with a specific activity of 546 MBq/mmol Copyright © 2002 John Wiley & Sons, Ltd.
Synthesis of N‐(piperidin‐1‐yl)‐5‐(4‐methoxyphenyl)‐1‐(2‐chlorophenyl)‐4‐[18F]fluoro‐1H‐pyrazole‐3‐carboxamide by nucleophilic [18F] fluorination: a PET radiotracer for studying CB1 cannabinoid receptors
Authors: Katoch‐Rouse Reeti , Horti Andrew G. 
Published: January 2003

AbstractThe feasibility of nucleophilic displacement of bromide in the 4‐bromopyrazole ring with [18F]fluoride has been demonstrated by the synthesis of two radiolabeled compounds: N‐(piperidin‐1‐yl)‐5‐(4‐methoxyphenyl)‐1‐(2‐chlorophenyl)‐4‐[18F]fluoro‐1H‐pyrazole‐3‐carboxamide, ([18F] NIDA‐42033) 1b and 1‐(2‐chlorophenyl)‐4‐[18F]fluoro‐5‐(4‐methoxyphenyl)‐1H‐pyrazole‐3‐carboxylic acid, ethyl ester 4. The radiochemical yields were in the range of 1–6%. [18F]NIDA‐42033, a potential radiotracer for the study of CB1 cannabinoid receptors in the animal brain by positron emission tomography, has been synthesized in sufficient quantities with specific radioactivity greater than 2500 mCi/μmol and radiochemical purity >95%. Copyright © 2002 John Wiley & Sons, Ltd.
Preparation of 1,2,3,4,6‐penta‐O‐galloyl‐[U‐14C]‐D‐glucopyranose
Authors: Chen Yumin , E. Hagerman Ann , E. Minto Robert 
Published: January 2003

AbstractThe synthesis of 1,2,3,4,6‐penta‐O‐galloyl‐[U‐14C]‐D‐glucopyranose is described. [U‐14C] glucopyranose was reacted with tri‐O‐benzylgallic acid forming 1,2,3,4,6‐penta(tri‐O‐benzylgalloyl)‐[U‐14C]‐D‐glucopyranose as chromatograpically separable anomers. Removal of the benzyl group by catalytic hydrogenation afforded 1,2,3,4,6‐penta‐O‐galloyl‐[U‐14C]‐D‐glucopyranose in 54% overall yield. Copyright © 2002 John Wiley & Sons, Ltd.