Search Results - (Author, Cooperation:F. Piehl)
-
1Latest Papers from Table of Contents or Articles in PressS. Sawcer ; G. Hellenthal ; M. Pirinen ; C. C. Spencer ; N. A. Patsopoulos ; L. Moutsianas ; A. Dilthey ; Z. Su ; C. Freeman ; S. E. Hunt ; S. Edkins ; E. Gray ; D. R. Booth ; S. C. Potter ; A. Goris ; G. Band ; A. B. Oturai ; A. Strange ; J. Saarela ; C. Bellenguez ; B. Fontaine ; M. Gillman ; B. Hemmer ; R. Gwilliam ; F. Zipp ; A. Jayakumar ; R. Martin ; S. Leslie ; S. Hawkins ; E. Giannoulatou ; S. D'Alfonso ; H. Blackburn ; F. Martinelli Boneschi ; J. Liddle ; H. F. Harbo ; M. L. Perez ; A. Spurkland ; M. J. Waller ; M. P. Mycko ; M. Ricketts ; M. Comabella ; N. Hammond ; I. Kockum ; O. T. McCann ; M. Ban ; P. Whittaker ; A. Kemppinen ; P. Weston ; C. Hawkins ; S. Widaa ; J. Zajicek ; S. Dronov ; N. Robertson ; S. J. Bumpstead ; L. F. Barcellos ; R. Ravindrarajah ; R. Abraham ; L. Alfredsson ; K. Ardlie ; C. Aubin ; A. Baker ; K. Baker ; S. E. Baranzini ; L. Bergamaschi ; R. Bergamaschi ; A. Bernstein ; A. Berthele ; M. Boggild ; J. P. Bradfield ; D. Brassat ; S. A. Broadley ; D. Buck ; H. Butzkueven ; R. Capra ; W. M. Carroll ; P. Cavalla ; E. G. Celius ; S. Cepok ; R. Chiavacci ; F. Clerget-Darpoux ; K. Clysters ; G. Comi ; M. Cossburn ; I. Cournu-Rebeix ; M. B. Cox ; W. Cozen ; B. A. Cree ; A. H. Cross ; D. Cusi ; M. J. Daly ; E. Davis ; P. I. de Bakker ; M. Debouverie ; B. D'Hooghe M ; K. Dixon ; R. Dobosi ; B. Dubois ; D. Ellinghaus ; I. Elovaara ; F. Esposito ; C. Fontenille ; S. Foote ; A. Franke ; D. Galimberti ; A. Ghezzi ; J. Glessner ; R. Gomez ; O. Gout ; C. Graham ; S. F. Grant ; F. R. Guerini ; H. Hakonarson ; P. Hall ; A. Hamsten ; H. P. Hartung ; R. N. Heard ; S. Heath ; J. Hobart ; M. Hoshi ; C. Infante-Duarte ; G. Ingram ; W. Ingram ; T. Islam ; M. Jagodic ; M. Kabesch ; A. G. Kermode ; T. J. Kilpatrick ; C. Kim ; N. Klopp ; K. Koivisto ; M. Larsson ; M. Lathrop ; J. S. Lechner-Scott ; M. A. Leone ; V. Leppa ; U. Liljedahl ; I. L. Bomfim ; R. R. Lincoln ; J. Link ; J. Liu ; A. R. Lorentzen ; S. Lupoli ; F. Macciardi ; T. Mack ; M. Marriott ; V. Martinelli ; D. Mason ; J. L. McCauley ; F. Mentch ; I. L. Mero ; T. Mihalova ; X. Montalban ; J. Mottershead ; K. M. Myhr ; P. Naldi ; W. Ollier ; A. Page ; A. Palotie ; J. Pelletier ; L. Piccio ; T. Pickersgill ; F. Piehl ; S. Pobywajlo ; H. L. Quach ; P. P. Ramsay ; M. Reunanen ; R. Reynolds ; J. D. Rioux ; M. Rodegher ; S. Roesner ; J. P. Rubio ; I. M. Ruckert ; M. Salvetti ; E. Salvi ; A. Santaniello ; C. A. Schaefer ; S. Schreiber ; C. Schulze ; R. J. Scott ; F. Sellebjerg ; K. W. Selmaj ; D. Sexton ; L. Shen ; B. Simms-Acuna ; S. Skidmore ; P. M. Sleiman ; C. Smestad ; P. S. Sorensen ; H. B. Sondergaard ; J. Stankovich ; R. C. Strange ; A. M. Sulonen ; E. Sundqvist ; A. C. Syvanen ; F. Taddeo ; B. Taylor ; J. M. Blackwell ; P. Tienari ; E. Bramon ; A. Tourbah ; M. A. Brown ; E. Tronczynska ; J. P. Casas ; N. Tubridy ; A. Corvin ; J. Vickery ; J. Jankowski ; P. Villoslada ; H. S. Markus ; K. Wang ; C. G. Mathew ; J. Wason ; C. N. Palmer ; H. E. Wichmann ; R. Plomin ; E. Willoughby ; A. Rautanen ; J. Winkelmann ; M. Wittig ; R. C. Trembath ; J. Yaouanq ; A. C. Viswanathan ; H. Zhang ; N. W. Wood ; R. Zuvich ; P. Deloukas ; C. Langford ; A. Duncanson ; J. R. Oksenberg ; M. A. Pericak-Vance ; J. L. Haines ; T. Olsson ; J. Hillert ; A. J. Ivinson ; P. L. De Jager ; L. Peltonen ; G. J. Stewart ; D. A. Hafler ; S. L. Hauser ; G. McVean ; P. Donnelly ; A. Compston
Nature Publishing Group (NPG)
Published 2011Staff ViewPublication Date: 2011-08-13Publisher: Nature Publishing Group (NPG)Print ISSN: 0028-0836Electronic ISSN: 1476-4687Topics: BiologyChemistry and PharmacologyMedicineNatural Sciences in GeneralPhysicsKeywords: Alleles ; Cell Differentiation/immunology ; Europe/ethnology ; Genetic Predisposition to Disease/*genetics ; Genome, Human/genetics ; Genome-Wide Association Study ; HLA-A Antigens/genetics ; HLA-DR Antigens/genetics ; HLA-DRB1 Chains ; Humans ; Immunity, Cellular/genetics/*immunology ; Major Histocompatibility Complex/genetics ; Multiple Sclerosis/*genetics/*immunology ; Polymorphism, Single Nucleotide/genetics ; Sample Size ; T-Lymphocytes, Helper-Inducer/cytology/immunologyPublished by: -
2Articles: DFG German National LicensesGielen, A. ; Khademi, M. ; Muhallab, S. ; Olsson, T. ; Piehl, F.
Oxford, UK : Blackwell Science Ltd
Published 2003Staff ViewISSN: 1365-3083Source: Blackwell Publishing Journal Backfiles 1879-2005Topics: MedicineNotes: Central nervous system (CNS)-autoreactive immune responses can exert neuroprotective effects, possibly mediated via the release of neurotrophic factors from infiltrating leucocytes. Herein, we analysed neurotrophin and cytokine mRNA levels using TaqMan polymerase chain reaction in unstimulated peripheral blood mononuclear cells (PBMCs) from multiple sclerosis (MS) patients in remission and controls. We demonstrate that mRNA for brain-derived neurotrophic factor (BDNF), but not neurotrophin-3 or nerve growth factor (NGF), is readily detectable in PBMC and that levels in MS are increased by approximately 60% compared with patients with other neurological diseases or healthy subjects. These results provide additional evidence that a potentially neuroprotective facet of autoimmune inflammation is present in MS.Type of Medium: Electronic ResourceURL: -
3Articles: DFG German National LicensesMuhallab, S. ; Lundberg, C. ; Gielen, A. W. ; Lidman, O. ; Svenningsson, A. ; Piehl, F. ; Olsson, T.
Oxford, UK : Blackwell Science Ltd
Published 2002Staff ViewISSN: 1365-3083Source: Blackwell Publishing Journal Backfiles 1879-2005Topics: MedicineNotes: Recent evidence suggests that autoimmune reactions in the central nervous system (CNS) not only have detrimental consequences but can also be neuroprotective, and that this effect is mediated by the expression of neuronal growth factors by infiltrating leucocytes. Here we dissect these two phenomena in guinea pig myelin basic protein peptide (gpMBP 63–88)-induced experimental autoimmune encephalomyelitis (EAE) in the Lewis rat. Real-time TaqMan polymerase chain reaction (PCR) was used to measure mRNA for the nerve growth factors, brain-derived neurotrophic factor (BDNF) and neurotrophin (NT)-3. As reference, the well-known proinflammatory mediator molecules interferon (IFN)-γ and tumour necrosis factor (TNF)-α were quantified. In whole lumbar cord tissue, both the nerve growth factors and the proinflammatory cytokines, IFN-γ and TNF-α, displayed similar expression patterns, peaking at the height of the disease. Among the infiltrating inflammatory cells isolated and sorted from the CNS, αβ+/T-cell receptor (TCR)BV8S2+, but not αβ+/TCRBV8S2–, recognized the encephalitogenic MBP peptide. Interestingly, these two populations displayed contrasting expression patterns of nerve growth factors and proinflammatory cytokines with higher inflammatory cytokine mRNA levels in αβ+/TCRBV8S2+ cells at all time intervals, whereas the levels of BDNF and NT3 were higher in αβ+/TCRBV8S2– cells. We conclude that a potentially important neuroprotective facet of CNS inflammation dominantly prevails within other non-MBP peptide-specific lymphoid cells and that there are independent regulatory mechanisms for neurotrophin and inflammatory cytokine expression during EAE.Type of Medium: Electronic ResourceURL: -
4Articles: DFG German National LicensesPiehl, F. ; Arvidsson, U. ; Johnson, H. ; Cullheim, S. ; Dagerlind, Å. ; Ulfhake, B. ; Cao, Y. ; Elde, R. ; Pettersson, R. F. ; Terenius, L. ; Hökfelt, T.
Oxford, UK : Blackwell Publishing Ltd
Published 1993Staff ViewISSN: 1460-9568Source: Blackwell Publishing Journal Backfiles 1879-2005Topics: MedicineNotes: The mRNA levels for growth-associated protein 43 (GAP-43), acidic fibroblast growth factor (aFGF), α and β-calcitonin gene-related peptide (CGRP), cholecystokinin (CCK) and choline acetyltransferase (ChAT) in rat lumbar spinal motoneurons were studied by in situ hybridization 1, 5 and 21 days and 20 weeks following unilateral peripheral nerve sectioning, ventral rhizotomy or dorsal rhizotomy. Furthermore, CGRP- and aFGF-like immunoreactivities in the ventral horn were studied using immunohistochemistry. One to 21 days after axotomy, GAP-43 and α-CGRP mRNAs increased in lesioned motoneurons, while the aFGF mRNA levels were marginally higher in motoneurons on the lesion side as compared to the control side. β-CGRP, CCK and ChAT mRNA levels, on the other hand, decreased during the short-term response (1 – 21 days) to axotomy. After ventral rhizotomy, but not peripheral axotomy, there was complete disappearance of aFGF-like immunoreactivity in the ventral root proximal to the lesion. In animals subjected to long-term survival (20 weeks) after peripheral axotomy, the expression of all studied substances had returned to normal levels. Unilateral dorsal rhizotomy did not induce any substantial short- or long-term shifts in the cellular expression of the GAP-43, aFGF, CGRP and CCK peptides or their mRNAs in motoneurons of lesioned segments. These results indicate that peptides/proteins in motoneurons are expressed differentially after axotomy. Whereas α-CGRP and GAP-43 are up-regulated, CCK and β-CGRP become down-regulated and aFGF is largely unaffected.Type of Medium: Electronic ResourceURL: -
5Articles: DFG German National LicensesJi, R.-R. ; Zhang, Q. ; Zhang, X. ; Piehl, F. ; Reilly, T. ; Pettersson, R. F. ; Hökfelt, T.
Oxford, UK : Blackwell Publishing Ltd
Published 1995Staff ViewISSN: 1460-9568Source: Blackwell Publishing Journal Backfiles 1879-2005Topics: MedicineNotes: Using quantitative in situ hybridization and immunohistochemistry the expression of acidic and basic fibroblast growth factors (aFGF, bFGF) in dorsal root ganglia (DRGs) was examined. Around 5% of the small neurons expressed bFGF mRNA in normal DRGs. Nerve injury induced a very dramatic and rapid up-regulation in bFGF mRNA levels, and around 80% of all DRG neurons expressed bFGF mRNA 3 days after axotomy. A distinct increase in bFGF-like immunoreactivity (LI) was also detected as early as 15 h after axotomy. The elevation of bFGF mRNA and protein levels declined after 1 week. bFGF mRNA was also up-regulated in non-neuronal cells following axotomy. Normally bFGF-LI was mainly localized in the nuclei of DRG neurons and in some non-neuronal cells. After nerve section, bFGF-LI was in addition found in the cytoplasm, and many more bFGF-positive non-neuronal cells were observed. By means of confocal microscopy analysis of axotomized DRGs, some bFGF-LI could be detected in vesicle-like structures in the cytoplasm as well as in the nucleoli, in addition to the nuclear location. Application of leukaemia inhibitory factor to the transected sciatic nerve significantly increased the number of bFGF-positive neurons, whereas the bFGF-LI in non-neuronal cells was strongly suppressed. About 70% of the normal DRG neurons expressed aFGF mRNA and aFGF-LI. Axotomy produced a moderate increase in aFGF mRNA levels, but no detectable effect on protein levels. Taken together, the results show that bFGF may be involved in the neuronal response to injury and suggest a role in neuronal survival and regeneration in axotomized DRG neurons.Type of Medium: Electronic ResourceURL: -
6Articles: DFG German National LicensesHokfelt, T. ; Cortes, R. ; Villar, M. ; Dagerlind, Å. ; Arvidsson, U. ; Piehl, F. ; Johnson, H. ; Cullheim, S. ; Ulfhake, B. ; Terenius, L. ; Xu, X.-J. ; Wiesenfeld-Hallin, Z.
Amsterdam : ElsevierStaff ViewISSN: 0167-0115Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002Topics: MedicineType of Medium: Electronic ResourceURL: -
7Articles: DFG German National LicensesZhang, X. ; Verge, V. M. K. ; Wiesenfeld-Hallin, Z. ; Piehl, F. ; Hökfelt, T.
Springer
Published 1993Staff ViewISSN: 1432-1106Keywords: Plasticity ; Enkephalin ; Vasoactive intestinal polypeptide ; Somatostatin ; Neuropeptide tyrosineSource: Springer Online Journal Archives 1860-2000Topics: MedicineNotes: Abstract The extent to which the plasticity in peptide expression observed in developing spinal motoneurons occurs following proximal peripheral axotomy in the adult rat was examined using in situ hybridization and immunohistochemical techniques to visualize the changes. Transient upregulation of galanin, vasoactive intestinal polypeptide (VIP) and substance P messenger ribonucleic acids (mRNAs) was observed within subpopulations of motoneurons ipsilateral to lesion for periods lasting 2–3 weeks after injury. In contrast, the axotomy-induced heterogenous increases in somatostatin and neuropeptide tyrosine mRNA expression in ipsilateral motoneurons remained elevated, or, in the case of somatostatin, continued to increase for the time period studied (1 month). Immunohistochemical analysis agreed with the in situ hybridization results, showing some motoneurons within the injured ventral horn to contain galanin-, VIP-or somatostatin-like immunoreactivity. In some instances, galanin-immunoreactive motoneurons colocalized with calcitonin gene-related peptide immunoreactivity. Most of the neurons expressing the injury-induced peptides appeared large, presumably alpha-motoneurons, but there were also many small neurons expressing galanin in the ventral horn ipsilateral to lesion. This may represent evidence for peptide synthesis in gamma-motoneurons. The only peptide mRNA studied to be downregulated in response to axotomy was enkephalin. The results show that peptide expression in injured motoneurons is dramatically altered, the significance of which remains to be determined.Type of Medium: Electronic ResourceURL: -
8Articles: DFG German National LicensesLindå, H. ; Piehl, F. ; Dagerlind, Å. ; Verge, V. M. K. ; Arvidsson, U. ; Cullheim, S. ; Risling, M. ; Ulfhake, B. ; Hökfelt, T.
Springer
Published 1992Staff ViewISSN: 1432-1106Keywords: GAP-43 ; In situ hybridization ; Spinal cord ; Axotomy ; Rat ; Cat ; MonkeySource: Springer Online Journal Archives 1860-2000Topics: MedicineNotes: Summary In situ hybridization histochemistry was used to detect cell bodies expressing mRNA encoding for the phosphoprotein GAP-43 in the lumbosacral spinal cord of the adult rat, cat and monkey under normal conditions and, in the cat and rat, also after different types of lesions. In the normal spinal cord, a large number of neurons throughout the spinal cord gray matter were found to express GAP-43 mRNA. All neurons, both large and small, in the motor nucleus (Rexed's lamina IX) appeared labeled, indicating that both alpha and gamma motoneurons express GAP-43 mRNA under normal conditions. After axotomy by an incision in the ventral funiculus or a transection of ventral roots or peripheral nerves, GAP-43 mRNA was clearly upregulated in axotomized motoneurons, including both alpha and gamma motoneurons. An increase in GAP-43 mRNA expression was already detectable 24 h postoperatively in lumbar motoneurons both after a transection of the sciatic nerve at knee level and after a transection of ventral roots. At this time, a stronger response was seen in the motoneurons which had been subjected to the distal sciatic nerve transection than was apparent for the more proximal ventral root lesion. An upregulation of GAP-43 mRNA could also be found in intact motoneurons located on the side contralateral to the lesion, but only after a peripheral nerve transection, indicating that the concomitant influence of dorsal root afferents may play a role in GAP-43 mRNA regulation. However, a dorsal root transection alone did not seem to have any detectable influence on the expression of GAP-43 mRNA in spinal motoneurons, while the neurons located in the superficial laminae of the dorsal horn responded with an upregulation of GAP-43 mRNA. The presence of high levels of GAP-43 in neurons has been correlated with periods of axonal growth during both development and regeneration. The role for GAP-43 in neurons under normal conditions is not clear, but it may be linked with events underlying remodelling of synaptic relationships or transmitter release. Our findings provide an anatomical substrate to support such a hypothesis in the normal spinal cord, and indicate a potential role for GAP-43 in axon regeneration of the motoneurons, since GAP-43 mRNA levels was strongly upregulated following both peripheral axotomy and axotomy within the spinal cord. The upregulation of GAP-43 mRNA found in contralateral, presumably uninjured motoneurons after peripheral nerve transection, as well as in dorsal horn neurons after a dorsal root transection, indicates that GAP-43 levels are altered not only as a direct consequence of a lesion, but also after changes in the synaptic input to the neurons.Type of Medium: Electronic ResourceURL: -
9Articles: DFG German National LicensesStaff View
ISSN: 1432-1106Keywords: Axotomy ; Retrograde tracing ; Spinal cord ; Motoneurons ; RatSource: Springer Online Journal Archives 1860-2000Topics: MedicineNotes: Abstract The content of calcitonin gene-related peptide-like immunoreactivity (CGRP-LI) in motoneurons was studied in four motor pools supplying muscles in the rat hind limb subserving different types of motor activity. The motor pools were identified by retrograde labeling with horseradish peroxidase or fluorophore-conjugated dextran amines, which were injected into the soleus, tibialis anterior, lateral gastrocnemius, or abductor digiti minimi muscles. After processing for immunohistochemistry, a semiquantitative evaluation was carried out to estimate the proportion of strongly, intermediately, and weakly labeled motoneurons, as well as motoneurons totally lacking CGRP staining. This revealed a considerable diversity in the intensity of CGRP labeling even for motoneurons in the same motoneuron pool. Thus, strongly labeled cells, as well as cells devoid of CGRP label, were found in all four motoneuron pools. However, a difference was found in the distribution of motoneurons innervating muscles with a dominant composition of fast and slow motor units, respectively, in that a larger fraction of the latter type lacked CGRP-LI. Moreover, generally motoneurons in the small motor units of the abductor digiti minimi muscle displayed weaker staining, and a larger proportion of cells was totally devoid of CGRP-LI (16%) compared with larger motor units of the other three muscles (1–10%). Small-sized cells within the γ-motoneuron size range were weakly stained or, more frequently, totally devoid of CGRP label (50%) as compared to larger cells, presumably representing α-motoneurons (1–16%). Five days after axotomy all four studied motoneuron pools displayed stronger CGRP labeling than corresponding unlesioned pools. However, a considerable variation in CGRP labeling persisted also among axotomized motoneurons. These results indicate that motoneurons normally display a great variation in CGRP-LI levels, but that motoneurons of small and slow-twitch motor units in general have lower levels than motoneurons of large and fast-twitch motor units, respectively. After axotomy, CGRP-LI increases in lesioned motoneuron pools compared with normal, but in a fraction of the axotomized motoneurons the increase seems to be discrete or even absent. The possible physiological implications of these findings are discussed.Type of Medium: Electronic ResourceURL: -
10Articles: DFG German National LicensesArvidsson, U. ; Johnson, H. ; Piehl, F. ; Cullheim, S. ; Hökfelt, T. ; Risling, M. ; Terenius, L. ; Ulfhake, B.
Springer
Published 1990Staff ViewISSN: 1432-1106Keywords: Neuropeptide ; Plasticity ; Nerve injury ; Spinal cord ; Immunohistochemistry ; Cat ; RatSource: Springer Online Journal Archives 1860-2000Topics: MedicineNotes: Summary By use of fluorescence immunohistochemistry it is shown that sciatic nerve section in cat and rat induces increased levels of immunoreactive calcitonin gene-related peptide (CGRP) in axotomized motoneurons. In the rat, this effect was clearly seen at 2–5 days postoperatively, but could not be demonstrated after 11–21 days. These findings are discussed in relation to previously proposed roles for CGRP in motoneurons.Type of Medium: Electronic ResourceURL: -
11Articles: DFG German National LicensesPiehl, F. ; Hammarberg, Henrik ; Tabar, Gabriella ; Hökfelt, Tomas ; Cullheim, Staffan
Springer
Published 1998Staff ViewISSN: 1432-1106Keywords: Key words Growth-associated protein-43 ; Galanin ; c-jun ; Low-affinity nerve growth factor receptor ; RatSource: Springer Online Journal Archives 1860-2000Topics: MedicineNotes: Abstract The axotomy reaction in motoneurons after a peripheral nerve transection in the adult animal is characterized by a robust upregulation of alpha-calcitonin gene-related peptide (CGRP) messenger RNA (mRNA) together with mRNAs encoding cytoskeletal and growth-related proteins. Here we have examined whether the nature of the lesion and the age of the animal have any impact on the mRNA regulation in severed cells. Thus, the effect of a sciatic nerve transection in the adult rat was compared with, on the one hand, ventral root avulsions in the adult animal and, on the other hand, sciatic nerve transection in the immature animal. In the two latter cases, a proportion of the lesioned cells die and overall chances of regeneration are small. In the adult animal a sciatic nerve transection induced an upregulation of alpha-CGRP mRNA from the 3rd day after surgery and throughout the first 3 weeks (the time span of the study). Also low-affinity nerve growth factor receptor (p75) and growth-associated protein-43 (GAP-43) mRNAs were upregulated during the entire 3-week period. In contrast, after ventral root avulsion, the expression of alpha-CGRP, c-jun, and p75 mRNAs were normalized within the 1st postoperative week, while GAP-43 mRNA was still upregulated at 3 weeks. Galanin message-associated peptide (GMAP) mRNA became upregulated preferentially in motoneurons subjected to ventral root avulsion, while nitric oxide synthase (NOS) mRNA was expressed exclusively after the latter type of injury. In the immature animal, alpha-CGRP mRNA was downregulated after sciatic nerve transection in rats aged 3 days or 7 days at the time of surgery; while, in contrast, an upregulation was seen in 12- or 21-day-old animals. GAP-43 and c-jun mRNAs were upregulated in lesioned motoneurons of all ages, while GMAP mRNA was upregulated preferentially in lesioned motoneurons of early postnatal animals. p75 mRNA was expressed in unlesioned immature motoneurons until the age of 7–10 days. The downregulation of p75 mRNA in intact cells at this age coincided with a developmental switch in the ability of axotomized cells to express increased levels of p75 mRNA. No expression of NOS mRNA was detectable in lesioned cells of any of the age groups. These results show that the age of the animal and the type of axonal injury are indeed to a high degree influencing the changes seen in the protein expression pattern in axotomized rat motoneurons. The different responses in these paradigms suggest differences in the trophic response from surrounding glia or the trophic responsiveness of lesioned motoneurons. Also, the results may indicate different roles for the studied substances during the regenerative response of lesioned neurons. Of the substances studied here, upregulation of alpha-CGRP and p75 mRNAs best correlated with a possibility of axon regeneration.Type of Medium: Electronic ResourceURL: