| 1. |
- Eriksson Linsmeier, Cecilia, et al.
(författare)
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Can histology solve the riddle of non-functioning electrodes; factors influencing the biocompatibillity of brain machine interfaces.
- 2011
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Ingår i: Progress in Brain Research. - 0079-6123. ; 194, s. 181-189
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Bokkapitel (refereegranskat)abstract
- Neural interfaces hold great promise to become invaluable clinical and diagnostic tools in the near future. However, the biocompatibility and the long-term stability of the implanted interfaces are far from optimized. There are several factors that need to be addressed and standardized when improving the long-term success of an implanted electrode. We have chosen to focus on three key factors when evaluating the evoked tissue responses after electrode implantation into the brain: implant size, fixation mode, and evaluation period. Further, we show results from an ultrathin multichannel wire electrode that has been implanted in the rat cerebral cortex for 1 year. To improve biocompatibility of implanted electrodes, we would like to suggest that free-floating, very small, flexible, and, in time, wireless electrodes would elicit a diminished cell encapsulation. We would also like to suggest standardized methods for the electrode design, the electrode implantation method, and the analyses of cell reactions after implantation into the CNS in order to improve the long-term success of implanted neural interfaces.
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| 2. |
- Abdesselam, A., et al.
(författare)
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Engineering for the ATLAS SemiConductor Tracker (SCT) end-cap
- 2008
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Ingår i: Journal of Instrumentation. - 1748-0221. ; 3
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Tidskriftsartikel (refereegranskat)abstract
- The ATLAS SemiConductor Tracker (SCT) is a silicon-strip tracking detector which forms part of the ATLAS inner detector. The SCT is designed to track charged particles produced in proton-proton collisions at the Large Hadron Collider (LHC) at CERN at an energy of 14 TeV. The tracker is made up of a central barrel and two identical end-caps. The barrel contains 2112 silicon modules, while each end-cap contains 988 modules. The overall tracking performance depends not only on the intrinsic measurement precision of the modules but also on the characteristics of the whole assembly, in particular, the stability and the total material budget. This paper describes the engineering design and construction of the SCT end-caps, which are required to support mechanically the silicon modules, supply services to them and provide a suitable environment within the inner detector. Critical engineering choices are highlighted and innovative solutions are presented - these will be of interest to other builders of large-scale tracking detectors. The SCT end-caps will be fully connected at the start of 2008. Further commissioning will continue, to be ready for proton-proton collision data in 2008.
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| 3. |
- Abdesselam, A., et al.
(författare)
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The ATLAS semiconductor tracker end-cap module
- 2007
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Ingår i: Nuclear Instruments and Methods in Physics Research Section A. - : Elsevier BV. - 0168-9002 .- 1872-9576. ; 575:3, s. 353-389
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Tidskriftsartikel (refereegranskat)abstract
- The challenges for the tracking detector systems at the LHC are unprecedented in terms of the number of channels, the required read-out speed and the expected radiation levels. The ATLAS Semiconductor Tracker. (SCT) end-caps have a total of about 3 million electronics channels each reading out every 25 ns into its own on-chip 3.3 mu s buffer. The highest anticipated dose after 10 years operation is 1.4x10(14) cm(-2) in units of 1 MeV neutron equivalent (assuming the damage factors scale with the non-ionising energy loss). The forward tracker has 1976 double-sided modules, mostly of area similar to 70 cm(2), each having 2 x 768 strips read out by six ASICs per side. The requirement to achieve an average perpendicular radiation length of 1.5% X-0, while coping with up to 7 W dissipation per module (after irradiation), leads to stringent constraints on the thermal design. The additional requirement of 1500e(-) equivalent noise charge (ENC) rising to only 1800e(-) ENC after irradiation, provides stringent design constraints on both the high-density Cu/Polyimide flex read-out circuit and the ABCD3TA read-out ASICs. Finally, the accuracy of module assembly must not compromise the 16 mu m (r phi) resolution perpendicular to the strip directions or 580 mu m radial resolution coming from the 40 mrad front-back stereo angle. A total of 2210 modules were built to the tight tolerances and specifications required for the SCT. This was 234 more than the 1976 required and represents a yield of 93%. The component flow was at times tight, but the module production rate of 40-50 per week was maintained despite this. The distributed production was not found to be a major logistical problem and it allowed additional flexibility to take advantage of where the effort was available, including any spare capacity, for building the end-cap modules. The collaboration that produced the ATLAS SCT end-cap modules kept in close contact at all times so that the effects of shortages or stoppages at different sites could be rapidly resolved.
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| 4. |
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| 5. |
- Bentzer, Peter, et al.
(författare)
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Supersensitivity in rat micro-arteries after short-term denervation
- 1997
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Ingår i: Acta Physiologica Scandinavica. - 0001-6772. ; 161:2, s. 125-133
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Tidskriftsartikel (refereegranskat)abstract
- Contractile responses to phenylephrine and high-K+ were investigated in vitro in microvascular preparations from the rat medial plantar artery, a branch from the saphenous artery, obtained after short-term denervation in vivo. Two groups of animals were studied: (1) animals undergoing surgical resection of the saphenous nerve, and (2) animals undergoing surgical resection of both the sciatic and saphenous nerves. The animals were operated on one side only. Microvascular preparations (diameter about 325 microns) were obtained 10 days after surgery. Vessels from the non-operated side served as controls. Immunocytochemistry showed a decreased number of both neuropeptide Y (NPY) and calcitonin gene-related peptide (CGRP) immunoreactive nerve fibres in vessels after resection of the saphenous nerve only. Resection of both the saphenous and the sciatic nerve caused a complete loss of immunoreactive nerve fibres. Mechanical measurements were performed using a wire myograph. In vessels subjected to resection of the saphenous nerve the sensitivity to phenylephrine was similar to controls. Vessels denervated by resection of both the saphenous and sciatic nerves showed significant increases in phenylephrine and potassium sensitivity. When depolarized in high-K+ solution the denervated vessels showed an increased sensitivity to extracellular Ca2+. The results show that complete short-term denervation of the rat medial plantar artery in vivo causes a pronounced supersensitivity in the vascular smooth muscle. The supersensitivity appears not to be restricted to the sympathetic alpha-receptors but also associated with changes in the cellular excitation-contraction coupling. Such altered reactivity of the vascular smooth muscle may contribute to vascular disturbances observed in vivo after nerve damage or surgical denervation.
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| 6. |
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| 7. |
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| 8. |
- Brekke, Helge R., et al.
(författare)
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Identification of p53 as a strong predictor of survival for patients with malignant peripheral nerve sheath tumors
- 2009
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Ingår i: Neuro-Oncology. - : Oxford University Press (OUP). - 1523-5866 .- 1522-8517. ; 11:5, s. 514-528
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Tidskriftsartikel (refereegranskat)abstract
- The purpose of this study was to identify new prognostic biomarkers with clinical impact in malignant peripheral nerve sheath tumor (MPNST), a highly aggressive malignancy for which no consensus therapy exists besides surgery. We have used tissue microarrays (TMAs) to assess in situ expression of 14 cell-cycle-regulating proteins in 64 well-characterized MPNST patients: 36 sporadic and 28 with neurofibromatosis type 1 (NF1). We developed a new software application for evaluation and logistics of the TMA images and performed a literature survey of cell cycle proteins in MPNST. For NF1-associated patients, there was a clear association between nuclear expression of p53 and poor survival (p = 0.004). Among the other proteins analyzed, we also found significant associations between survival and clinical variables, but none were as strong as that for p53. For the total series of MPNSTs, p53 was shown to be an independent predictor of survival, and patients without remission, with tumor size larger than 8 cm, and with positive p53 expression had a 60 times greater risk of dying within the first 5 years compared with the remaining patients (p = 0.000002). This is the most comprehensive study of in situ protein expression in MPNST so far, and expressed p53 was found to be a strong surrogate marker for outcome. Patients in complete remission with a primary p53-positive MPNST diagnosis may be considered in a high-risk subgroup and candidates for adjuvant treatment. Neuro-Oncology 11, 514-528, 2009 (Posted to Neuro-Oncology [serial online], Doc. D08-00271, January 30, 2009.)
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| 9. |
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| 10. |
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| 11. |
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| 12. |
- Danielsen, Nils, et al.
(författare)
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Inflammatory cells and mediators in the silicone chamber model for nerve regeneration
- 1993
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Ingår i: Biomaterials. - 0142-9612. ; 14:15, s. 5-1180
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Tidskriftsartikel (refereegranskat)abstract
- In the present study the inflammatory response was quantitatively evaluated during peripheral nerve regeneration. The fluid from silicone nerve regeneration chambers, inserted in rats, was collected during the early period of regeneration of transected sciatic nerves (6 h-7 d) and analysed with respect to inflammatory cells and mediators (leukotriene B4, LTB4, and interleukin-1 alpha, IL-1 alpha). Leucocytes were detected during the entire period (up to 7 d after implantation). The highest concentration was detected after 24 h. PMNG (polymorphonuclear granulocyte) was the predominant cell type in the chamber fluid during the initial 5d of regeneration. Analysis of the concentration of LTB4 demonstrated two peaks (at 24 h and 5 d). The IL-1 alpha concentration displayed an early and relatively smaller peak after 24 h and a second and much larger peak after 7 d, concomitant with an increase of the number of mononuclear cells.
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| 13. |
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| 14. |
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| 15. |
- Danielsen, Nils, et al.
(författare)
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The effects of delayed nerve repair on nerve regeneration in a silicone chamber model
- 1994
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Ingår i: Restorative Neurology and Neuroscience. - 0922-6028. ; 6:4, s. 317-322
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Tidskriftsartikel (refereegranskat)abstract
- The silicone chamber model for nerve regeneration is suitable to test the effects of exogenous agents or surgical manipulations on nerve regeneration. The total 16-day regeneration period used in this model makes it possible to analyze the effects of certain manipulations on the sequential advancement of the individual cellular components (circumferential perineurial-like cells, vessels, Schwann cells, axons, and myelin) into the chamber fibrin matrix. In the present study we compared the effects on cellular migration of a 7 day delayed chamber repair vs. chamber repair immediately after transection (control chambers) of the rat sciatic nerve. Regeneration was evaluated with light and electron microscopic techniques. Chambers implanted after a delay of 7 days had a statistically significant more advanced migration of vessels, Schwann cells, and axons from the proximal nerve stump and also a significantly increased vascular density as compared to control chambers. We conclude that a 7 day delayed nerve repair stimulates nerve regeneration in this specific silicone chamber model.
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| 16. |
- Edgren, Gudrun, et al.
(författare)
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Comparing the educational environment (as measured by DREEM) at two different stages of curriculum reform.
- 2010
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Ingår i: Medical Teacher. - : Informa UK Limited. - 0142-159X .- 1466-187X. ; 32:6, s. 233-238
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The medical programme at Lund University, Sweden, has undergone curricular reform over several stages, which is still ongoing. Students have been somewhat negative in their evaluations of the education during this time. AIM: To find out how the students perceived the educational climate using the Dundee Ready Education Environment Measure (DREEM), and to compare the findings taken at two given points in time. METHOD: The DREEM instrument was distributed in semesters 2, 6 and 10 in 2003 and 2005, to a total of 503 students. RESULTS: The students rated their climate as positive. The total DREEM score (145) was somewhat higher than other published results and in the same range as for other reformed curricula. There was hardly any difference between the genders in their perceptions of the climate. Certain items were rated low and became subject of development between the measurements. These items concerned a perceived lack of a support system for stressed students and a lack of feedback and constructive criticism from teachers. Some improvement was detected in 2005. CONCLUSION: The educational climate was high in a reformed curriculum and could be maintained high during on-going curricular reform. Educational development resulted in better results on some items.
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| 17. |
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| 18. |
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| 19. |
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| 20. |
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| 21. |
- Eriksson Linsmeier, Cecilia, et al.
(författare)
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Nanowire Biocompatibility in the Brain - Looking for a Needle in a 3D Stack.
- 2009
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Ingår i: Nano Letters. - : American Chemical Society (ACS). - 1530-6992 .- 1530-6984. ; 9:12, s. 4184-4190
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Tidskriftsartikel (refereegranskat)abstract
- We investigated the brain-tissue response to nanowire implantations in the rat striatum after 1, 6, and 12 weeks using immunohistochemistry. The nanowires could be visualized in the scar by confocal microscopy (through the scattered laser light). For the nanowire-implanted animals, there is a significant astrocyte response at week 1 compared to controls. The nanowires are phagocytized by ED1 positive microglia, and some of them are degraded and/or transported away from the brain.
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| 22. |
- Eriksson Linsmeier, Cecilia, et al.
(författare)
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Soft tissue reactions evoked by implanted gallium phosphide.
- 2008
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Ingår i: Biomaterials. - : Elsevier BV. - 1878-5905 .- 0142-9612. ; 29:35, s. 4598-4604
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Tidskriftsartikel (refereegranskat)abstract
- Neural devices may play an important role in the diagnosis and therapy of several clinical conditions, such as stroke, trauma or neurodegenerative disorders, by facilitating motor and pain control. Such interfaces, chronically implanted in the CNS, need to be biocompatible and have the ability to stimulate and record nerve signals. However, neural devices of today are not fully optimized. Nanostructured surfaces may improve electrical properties and lower evoked tissue responses. Vertical gallium phosphide (GaP) nanowires epitaxially grown from a GaP surface is one way of creating nanostructured electrodes. Thus, we chose to study the soft tissue reactions evoked by GaP surfaces. GaP and the control material titanium (Ti) were implanted in the rat abdominal wall for evaluation of tissue reactions after 1, 6, or 12 weeks. The foreign-body response was evaluated by measuring the reactive capsule thickness and by quantification of ED1-positive macrophages and total cells in the capsule. Furthermore, the concentration of Ga was measured in blood, brain, liver and kidneys. Statistically significant differences were noticed between GaP and Ti at 12 weeks for total and ED1-positive cell densities in the capsule. The chemical analysis showed that the concentration of Ga in brain, liver and kidneys increased during 12 weeks of implantation, indicating loss of Ga from the implant. Taken together, our results show that the biocompatible properties of GaP are worse than those of the well-documented biomaterial Ti.
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| 23. |
- Etemadi, Leila, et al.
(författare)
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UVB irradiation induces contralateral changes in galanin, substance P and c-fos immunoreactivity in rat dorsal root ganglia, dorsal horn and lateral spinal nucleus
- 2021
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Ingår i: Peptides. - : Elsevier BV. - 0196-9781. ; 136
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Tidskriftsartikel (refereegranskat)abstract
- The selection of control group is crucial, as the use of an inadequate group may strongly affect the results. In this study we examine the effect on contralateral tissue protein levels, in a model of unilateral UVB irradiation, as the contralateral side is commonly used as a control. Previous studies have shown that UVB irradiation increases immunoreactivity for inflammatory regulated neuropeptides. Unilateral UVB irradiation of rat hind paw was performed and corresponding contralateral spinal cord and dorsal root ganglia (DRG) were collected 2–96 h after and investigated for changes in galanin, substance P and c-fos immunoreactivity. Control tissue was collected from naïve rats. Measurement of skin blood flow from contralateral heel hind paws (Doppler), revealed no change compared to naïve rats. However, UVB irradiation caused a significant reduction in the contralateral proportion of galanin immunopositive DRG neurons, at all-time points, as well as an increase in the contralateral spinal cord dorsal horn, around the central canal and in the lateral spinal nucleus (2–48 h). The contralateral proportion of SP positive DRG neurons and dorsal horn immunoreactivity was unchanged, whereas the lateral spinal nucleus area showed increased immunoreactivity (48 h). UVB irradiation also induced a slight contralateral upregulation of c-fos in the dorsal horn/central canal area (24 and 48 h). In summary, unilateral UVB irradiation induced contralateral changes in inflammatory/nociceptive neuropeptides in spinal cord and afferent pathways involved in pain signaling already within 24 h, a time point when also ipsilateral neurochemical/physiological changes have been reported for rats and humans.
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| 24. |
- Etemadi, Leila, et al.
(författare)
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UVB irradiation induces rapid changes in galanin, substance P and c-fos immunoreactivity in rat dorsal root ganglia and spinal cord
- 2017
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Ingår i: Peptides. - : Elsevier BV. - 0196-9781. ; 87, s. 71-83
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Tidskriftsartikel (refereegranskat)abstract
- Recent studies have shown that UVB irradiation induces primary and secondary hyperalgesia in rats and humans peaking about 24 h after UVB exposure. In the present study we investigated the changes in galanin, substance P and c-fos immunoreactivity in rat DRG and spinal cord at the L5 level 2–96 h after UVB irradiation. UVB irradiation of the heel area in rats almost increased the skin blood flow two-fold 24 h after irradiation as measured by laser Doppler technique. UVB irradiation induced a significant reduction of the proportion of galanin positive DRG neurons for all time points, except at 12 h. In the spinal cord, UVB irradiation induced increased immunoreactivity for galanin in the dorsal horn, the area around the central canal and interestingly also in the lateral spinal nucleus 12–96 h after exposure. For substance P the proportion of substance P positive neurons was unchanged but UVB irradiation induced increased substance P immunoreactivity in the dorsal part of the spinal cord 48 h after irradiation. UVB irradiation also induced c-fos immunoreactivity in the dorsal horn and the area around the central canal 24 and 48 h after exposure. This translational model of UVB irradiation will induce rapid changes of neuropeptides implicated in nociceptive signaling in areas known to be of importance for nociception in a time frame, about 24 h after exposure, where also neurophysiological alteration have been described in humans and rats.
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| 25. |
- Geremia, Nicole M., et al.
(författare)
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Endogenous BDNF regulates induction of intrinsic neuronal growth programs in injured sensory neurons
- 2010
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Ingår i: Experimental Neurology. - : Elsevier BV. - 0014-4886. ; 223:1, s. 128-142
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Tidskriftsartikel (refereegranskat)abstract
- Identification of the molecule(s) that globally induce a robust regenerative state in sensory neurons following peripheral nerve injury remains elusive. A potential candidate is brain-derived neurotrophic factor (BDNF), the sole neurotrophin upregulated in sensory neurons after peripheral nerve injury. Here we tested the hypothesis that BDNF plays a critical role in the regenerative response of mature rat sensory neurons following peripheral nerve lesion. Neutralization of endogenous BDNF was performed by infusing BDNF antibodies intrathecally via a mini-osmotic pump for 3 days at the level of the fifth lumbar dorsal root ganglion, immediately following unilateral spinal nerve injury. This resulted in decreased expression of the injury/regeneration-associated genes growth-associated protein-43 and T alpha 1 tubulin in the injured sensory neurons as compared to injury plus control IgG infused or injury alone animals. Similar results were observed following inhibition of BDNF expression by intrathecal delivery of small interfering RNAs (siRNA) targeting BDNF starting 3 days prior to injury. The reduced injury/regeneration-associated gene expression correlated with a significantly reduced intrinsic capacity of these neurons to extend neurites when assayed in vitro. In contrast, delayed infusion of BDNF antibody for 3 days beginning 1 week post-lesion had no discernible influence on the elevated expression of these regeneration-associated markers. These results support an important role for endogenous BDNF in induction of the cell body response in injured sensory neurons and their intrinsic ability to extend neurites, but BDNF does not appear to be necessary for maintaining the response once it is induced. (C) 2009 Elsevier Inc. All rights reserved.
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| 26. |
- Gällentoft, Lina, et al.
(författare)
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Impact of degradable nanowires on long-term brain tissue responses
- 2016
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Ingår i: Journal of Nanobiotechnology. - : Springer Science and Business Media LLC. - 1477-3155. ; 14:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: A promising approach to improve the performance of neural implants consists of adding nanomaterials, such as nanowires, to the surface of the implant. Nanostructured interfaces could improve the integration and communication stability, partly through the reduction of the cell-to-electrode distance. However, the safety issues of implanted nanowires in the brain need to be evaluated and understood before nanowires can be used on the surface of implants for long periods of time. To this end we here investigate whether implanted degradable nanowires offer any advantage over non-degradable nanowires in a long-term in vivo study (1 year) with respect to brain tissue responses. Results: The tissue response after injection of degradable silicon oxide (SiOx)-coated gallium phosphide nanowires and biostable hafnium oxide-coated GaP nanowires into the rat striatum was compared. One year after nanowire injection, no significant difference in microglial or astrocytic response, as measured by staining for ED1 and glial fibrillary acidic protein, respectively, or in neuronal density, as measured by staining for NeuN, was found between degradable and biostable nanowires. Of the cells investigated, only microglia cells had engulfed the nanowires. The SiOx-coated nanowire residues were primarily seen in aggregated hypertrophic ED1-positive cells, possibly microglial cells that have fused to create multinucleated giant cells. Occasionally, degradable nanowires with an apparently intact shape were found inside single, small ED1-positive cells. The biostable nanowires were found intact in microglia cells of both phenotypes described. Conclusion: The present study shows that the degradable nanowires remain at least partly in the brain over long time periods, i.e. 1 year; however, no obvious bio-safety issues for this degradable nanomaterial could be detected.
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| 27. |
- Gällentoft, Lina, et al.
(författare)
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Size-dependent long-term tissue response to biostable nanowires in the brain.
- 2015
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Ingår i: Biomaterials. - : Elsevier BV. - 1878-5905 .- 0142-9612. ; 42, s. 172-183
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Tidskriftsartikel (refereegranskat)abstract
- Nanostructured neural interfaces, comprising nanotubes or nanowires, have the potential to overcome the present hurdles of achieving stable communication with neuronal networks for long periods of time. This would have a strong impact on brain research. However, little information is available on the brain response to implanted high-aspect-ratio nanoparticles, which share morphological similarities with asbestos fibres. Here, we investigated the glial response and neuronal loss in the rat brain after implantation of biostable and structurally controlled nanowires of different lengths for a period up to one year post-surgery. Our results show that, as for lung and abdominal tissue, the brain is subject to a sustained, local inflammation when biostable and high-aspect-ratio nanoparticles of 5 μm or longer are present in the brain tissue. In addition, a significant loss of neurons was observed adjacent to the 10 μm nanowires after one year. Notably, the inflammatory response was restricted to a narrow zone around the nanowires and did not escalate between 12 weeks and one year. Furthermore, 2 μm nanowires did not cause significant inflammatory response nor significant loss of neurons nearby. The present results provide key information for the design of future neural implants based on nanomaterials.
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| 28. |
- Haglid, Kenneth G, et al.
(författare)
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S-100beta stimulates neurite outgrowth in the rat sciatic nerve grafted with acellular muscle transplants
- 1997
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Ingår i: Brain Research. - 1872-6240. ; 753:2, s. 196-201
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Tidskriftsartikel (refereegranskat)abstract
- S-100beta promotes neurite extension in vitro and motoneuron survival in the chicken embryo. We demonstrate here that local administration of S-100beta stimulates the sciatic nerve regeneration into acellular muscle grafts. Normally there is a 8-10 day delay in the regeneration of axons into such grafts. Local administration of S-100beta (0.5-1.0 microg/h) significantly stimulated regeneration into the grafts. In S-100beta treated grafts, the regeneration distance was increased with a factor of about 2.3 times as compared to vehicle treated grafts. The distance of regeneration was monitored with pinch test which detects sensory axons. Regenerating axons were growing outside the necrotic muscle cells as revealed with immunohistochemistry for the neurofilament light weight polypeptide. S-100beta was demonstrated immunocytochemically in motor neurons of the rat lumbar spinal cord and in large and medium sized neurons of the dorsal root ganglia. The results suggest that S-100beta is a physiological growth factor for peripheral nerve axons.
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| 29. |
- Hansson, H A, et al.
(författare)
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Evidence indicating trophic importance of IGF-I in regenerating peripheral nerves
- 1986
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Ingår i: Acta Physiologica Scandinavica. - : Wiley. - 0001-6772 .- 1365-201X. ; 126:4, s. 14-609
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Tidskriftsartikel (refereegranskat)abstract
- The mechanisms influencing regeneration of peripheral nerves are incompletely known, but growth factors are supposed to play a key role. In the present study, we demonstrate, with the aid of immunohistochemical methods, that somatomedin C (Sm-C/insulin-like growth factor I/IGF-I) rapidly increased from low to high concentrations, reaching peak values in 2 weeks, in regenerating sciatic nerves of adult rats. In addition, IGF-I was demonstrated extracellularly, never observed in the control nerves. Reactive Schwann cells appeared to be the major source for IGF-synthesis. Higher concentrations were seen in tubulated nerves as compared to sutured ones. It is proposed that IGF-I exerts important growth supporting effects on regenerating peripheral nerves.
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| 30. |
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| 31. |
- Høland, Maren, et al.
(författare)
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Inferior survival for patients with malignant peripheral nerve sheath tumors defined by aberrant TP53
- 2018
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Ingår i: Modern Pathology. - : Elsevier BV. - 0893-3952. ; 31:11, s. 1694-1707
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Tidskriftsartikel (refereegranskat)abstract
- Malignant peripheral nerve sheath tumor is a rare and aggressive disease with poor treatment response, mainly affecting adolescents and young adults. Few molecular biomarkers are used in the management of this cancer type, and although TP53 is one of few recurrently mutated genes in malignant peripheral nerve sheath tumor, the mutation prevalence and the corresponding clinical value of the TP53 network remains unsettled. We present a multi-level molecular study focused on aberrations in the TP53 network in relation to patient outcome in a series of malignant peripheral nerve sheath tumors from 100 patients and 38 neurofibromas, including TP53 sequencing, high-resolution copy number analyses of TP53 and MDM2, and gene expression profiling. Point mutations in TP53 were accompanied by loss of heterozygosity, resulting in complete loss of protein function in 8.2% of the malignant peripheral nerve sheath tumors. Another 5.5% had MDM2 amplification. TP53 mutation and MDM2 amplification were mutually exclusive and patients with either type of aberration in their tumor had a worse prognosis, compared to those without (hazard ratio for 5-year disease-specific survival 3.5, 95% confidence interval 1.78–6.98). Both aberrations had similar consequences on the gene expression level, as analyzed by a TP53-associated gene signature, a property also shared with the copy number aberrations and/or loss of heterozygosity at the TP53 locus, suggesting a common “TP53-mutated phenotype” in as many as 60% of the tumors. This was a poor prognostic phenotype (hazard ratio = 4.1, confidence interval:1.7–9.8), thus revealing a TP53-non-aberrant patient subgroup with a favorable outcome. The frequency of the “TP53-mutated phenotype” warrants explorative studies of stratified treatment strategies in malignant peripheral nerve sheath tumor.
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| 32. |
- Jakobsson, Ulf, et al.
(författare)
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Psychometric evaluation of the Dundee Ready Educational Environment Measure: Swedish version.
- 2011
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Ingår i: Medical Teacher. - 0142-159X. ; 33:5, s. 267-274
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Tidskriftsartikel (refereegranskat)abstract
- Background: The Dundee Ready Educational Environment Measure (DREEM) has been used in various studies to evaluate the educational environment. However, psychometric evaluations of the instrument seem sparse, for all known versions of the instrument. Aim: The aim was to psychometrically evaluate the Swedish version of the DREEM instrument. Method: A total of 503 students (undergraduate medicine), aged 19-46 years, in semesters 2, 6 and 10 were included in the study. Validity was evaluated through analysis of construct validity and reliability. Results: The instrument had in general both acceptable validity and reliability. Due to a rather poor model fit in the confirmatory factor analysis, an explorative factor analysis was also employed which suggested a new five-factor solution for the instrument. Conclusions: The Swedish version of the DREEM instrument is shown to be valid and reliable, except for the factor structure. The new five-factor solution found in this study is not proven to be a superior measurement model compared with the original, but could be seen as an alternative model to the original, where the strong and weak areas are somewhat more easily identified.
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| 33. |
- Johansson, Fredrik I, et al.
(författare)
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Axonal outgrowth on nano-imprinted patterns
- 2006
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Ingår i: Biomaterials. - : Elsevier BV. - 1878-5905 .- 0142-9612. ; 27:8, s. 1251-1258
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Tidskriftsartikel (refereegranskat)abstract
- Nanotechnology has provided methods to fabricate surface patterns with features down to a few rim. If cells or cell processes exhibit contact guidance in response to such small patterns is an interesting question and could be pertinent for many applications. In the present study we investigated if axonal outgrowth was affected by nano-printed patterns in polymethylmethacrylate (PMMA)-covered silicon chips. To this end adult mouse sympathetic and sensory ganglia were mounted in Matrigel (R) on the chips close to the nano-patterns. The patterns consisted of parallel grooves with depths of 300 nm and varying widths of 100-400 nm. The distance between two adjacent grooves was 100-1600 nm. The chips were cultured in medium containing 25 ng/ml of nerve growth factor to stimulate axonal outgrowth. After 1 week of incubation. axonal outgrowth was investigated by immunocytochemistry or scanning electron microscopy. Axons displayed contact guidance on all patterns. Furthermore, we found that the nerve cell processes preferred to grow on ridge edges and elevations in the patterns rather than in grooves, a seemingly claustrophobic behavior. We conclude that axons of peripheral neurons might be guided by nanopatterns on PMMA when the lateral features are 100 nm or larger. The present results can be utilized for nerve regenerating scaffolds or the construction of a stable, high-resolution electronic interface to neurons, which is required for future brain machine interfaces. (c) 2005 Elsevier Ltd. All rights reserved.
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| 34. |
- Johansson, Fredrik, et al.
(författare)
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Porous silicon as a potential electrode material in a nerve repair setting: Tissue reactions.
- 2009
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Ingår i: Acta Biomaterialia. - : Elsevier BV. - 1878-7568 .- 1742-7061. ; 5, s. 2230-2237
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Tidskriftsartikel (refereegranskat)abstract
- We compared porous silicon (pSi) with smooth Si as chip-implant surfaces in a nerve regeneration setting. Silicon chips can be used for recording neural activity and are potential nerve interface devices. A silicon chip with one smooth and one porous side inserted into a tube was used to bridge a 5 mm defect in rat sciatic nerve. Six or 12 weeks later, new nerve structures surrounded by a perineurium-like capsule had formed on each side of the chip. The number of regenerated nerve fibers did not differ on either side of the chip as shown by immunostaining for neurofilaments. However, the capsule that had formed in contact with the chip was significantly thinner on the porous side than on the smooth side. Cellular protrusions had formed on the pSi side and the regenerated nerve tissue was found to attach firmly to this surface, while the tissue was hardly attached to the smooth silicon surface. We conclude that a pSi surface, due to its large surface area, diminished inflammatory response and firm adhesion to the tissue, should be a good material for the development of new implantable electronic nerve devices.
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| 35. |
- Jongsma, Helen, et al.
(författare)
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Markedly reduced chronic nociceptive response in mice lacking the PAC1 receptor
- 2001
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Ingår i: NeuroReport. - 1473-558X. ; 12:10, s. 2215-2219
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Tidskriftsartikel (refereegranskat)abstract
- The neuropeptide pituitary adenylate cyclase activating polypeptide (PACAP) has been proposed to have a role in nociception. Here we have used the formalin test, thermal laser stimulation and mechanical von Frey stimulation to investigate possible alteration of PAC1-/- mice nociceptive behaviour. Our finding, that PAC1-/- mice have a substantial, 75% decrease in nociceptive response during the late phase, provides clear evidence that the specific PACAP-receptor PAC1 is involved in the mediation of nociceptive responses during chronic conditions such as inflammation. PAC1-/- mice had small or no changes in the response to mechanical and thermal laser stimulation. This suggests a limited, if any, involvement of PAC1 in nociception after short-lasting stimuli. Injury-induced changes in DRG neuropeptide expression were more pronounced in PAC1-/- mice, implying neuroregulatory functions of PAC1.
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| 36. |
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| 37. |
- Jongsma Wallin, Helen, et al.
(författare)
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Exogenous NT-3 and NGF differentially modulate PACAP expression in adult sensory neurons, suggesting distinct roles in injury and inflammation
- 2001
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Ingår i: European Journal of Neuroscience. - : Wiley. - 1460-9568 .- 0953-816X. ; 14:2, s. 267-282
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Tidskriftsartikel (refereegranskat)abstract
- Expression of pituitary adenylate cyclase-activating polypeptide in sensory neurons varies with injury or inflammation. The neurotrophins NGF and NT-3 are profound regulators of neuronal peptidergic phenotype in intact and injured sensory neurons. This study examined their potential for modulation of PACAP expression in adult rat with intact and injured L4-L6 spinal nerves with or without immediate or delayed intrathecal infusion of NT-3 or NGF. Results indicate that in L5 DRG, few trkC neurons express high levels of PACAP mRNA in the intact state, but many do following injury. The elevated expression in injured neurons is mitigated by NT-3 infusion, suggesting a role for NT-3 in returning the 'injured phenotype' back towards an 'Intact phenotype'. NGF dramatically up-regulated PACAP expression in trkA-positive neurons in both intact and injured DRGs, implicating NGF as a positive regulator of PACAP expression in nociceptive neurons. Surprisingly, NT-3 modulates PACAP expression in an antagonistic fashion to NGF in intact neurons, an effect most evident in the trkA neurons not expressing trkC. Both NT-3 and NGF infusion results in decreased detection of PACAP protein in the region of the gracile nuclei, where central axons of the peripherally axotomized large sensory fibers terminate. NGF infusion also greatly increased the amount of PACAP protein detected in the portion of the dorsal horn innervated by small-medium size DRG neurons, while both neurotrophins appear able to prevent the decrease in PACAP expression observed in these afferents with injury. These results provide the first insights into the potential molecules implicated in the complex regulation of PACAP expression in sensory neurons.
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| 38. |
- Kerns, JM, et al.
(författare)
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A comparison of peripheral nerve regeneration in acellular muscle and nerve autografts
- 2003
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Ingår i: Scandinavian Journal of Plastic and Reconstructive Surgery and Hand Surgery. - : Informa UK Limited. - 1651-2073 .- 0284-4311. ; 37:4, s. 193-200
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Tidskriftsartikel (refereegranskat)abstract
- Regeneration of the rat sciatic nerve through acellular muscle and nerve autografts was evaluated 6-28 days postoperatively by the sensory pinch test, immunocytochemical staining for neurofilaments, and light and electron microscopy. Data points generated by the pinch test were plotted against postoperative time periods and by the use of regression analysis the initial delay period for muscle grafts was determined to 10.3 days. This value was similar to that previously published for acellular nerve grafts (9.5 days), but significantly longer than that for fresh nerve grafts (3.6 days). The calculated regeneration rate (slope of the regression line) for muscle grafts (1.8 mm/day) did not differ significantly ( p >0.05) from that calculated for acellular nerve grafts (2.1 mm/day) or for fresh nerve grafts (1.5 mm/day). The front of regenerating axons shown by axonal neurofilament staining confirmed the pinch test results. Both types of acellular grafts were repopulated with host non-neuronal cells and the muscle graft contained occasional ectopic muscle fibres. Remnants of graft basal laminae were evident at the ultrastructural level. These results indicate the suitability of either acellular muscle or nerve grafts for nerve repair despite their prolonged initial delay periods compared with conventional fresh nerve grafts.
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| 39. |
- Kerns, James, et al.
(författare)
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Effects of gradual bone lengthening on the rabbit tibial nerve
- 2001
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Ingår i: Scandinavian Journal of Plastic and Reconstructive Surgery and Hand Surgery. - : Informa UK Limited. - 1651-2073 .- 0284-4311. ; 35:4, s. 361-368
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Tidskriftsartikel (refereegranskat)abstract
- Little is known about the effect of gradual bone lengthening on peripheral nerves. In the present study, an external fixation device was applied to the rabbit tibia, which was then divided. After seven days, the tibia was subjected to 0.7 mm/day callus distraction for periods of up to one month. The tibial nerve was fixed in glutaraldehyde and plastic sections were cut in longitudinal and transverse planes for light and electron microscopy. Light microscopy showed a 64% increase in the gap length at the node of Ranvier in myelinated axons from the experimental side compared with the control side. The cross-sectional area of the non-myelinated axons was not altered significantly. We conclude that gradual stretching of the nerve elongates the nerve fibres at least at the region of the nodes, perhaps a point of least resistance. Diameters of fibres seem to be held more constant during the lengthening procedure.
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| 40. |
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| 41. |
- Kvist, Martin, et al.
(författare)
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Effects of FK506 on regeneration and macrophages in injured rat sciatic nerve.
- 2003
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Ingår i: Journal of the Peripheral Nervous System. - : Wiley. - 1085-9489 .- 1529-8027. ; 8:4, s. 251-259
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Tidskriftsartikel (refereegranskat)abstract
- Effects of FK506 [5.0 mg/kg body weight (BW), subcutaneous, daily] on nerve regeneration and presence of macrophages in lesioned rat sciatic nerves were studied. Models of autologous nerve graft or a nerve crush lesion were used and regeneration was evaluated by immunocytochemistry (also used to detect ED1/ED2 macrophages) and sensory pinch reflex test, respectively. Treatment with FK506 did not increase regeneration distance or regeneration rate in the autologous nerve grafts. However, regeneration distances after nerve crush were significantly longer following treatment with FK506. The number of macrophages (ED1/ED2) in nerve grafts increased over time, but treatment with FK506 had limited effects only in the presence of ED2 macrophages. Present and previously published studies may imply that there is a time-related and type-of-injury-related profile of FK506's pro-regenerative effect.
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| 42. |
- Lind, Gustav, et al.
(författare)
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Multiple implants do not aggravate the tissue reaction in rat brain.
- 2012
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 7:10
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Tidskriftsartikel (refereegranskat)abstract
- Chronically implanted microelectrodes are an invaluable tool for neuroscientific research, allowing long term recordings in awake and behaving animals. It is known that all such electrodes will evoke a tissue reaction affected by its' size, shape, surface structure, fixation mode and implantation method. However, the possible correlation between tissue reactions and the number of implanted electrodes is not clear. We implanted multiple wire bundles into the brain of rats and studied the correlation between the astrocytic and microglial reaction and the positioning of the electrode in relation to surrounding electrodes. We found that an electrode implanted in the middle of a row of implants is surrounded by a significantly smaller astrocytic scar than single ones. This possible interaction was only seen between implants within the same hemisphere, no interaction with the contralateral hemisphere was found. More importantly, we found no aggravation of tissue reactions as a result of a larger number of implants. These results highlight the possibility of implanting multiple electrodes without aggravating the glial scar surrounding each implant.
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| 43. |
- Lindgren, Stefan, et al.
(författare)
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Utbildning utan lottning
- 2006
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Ingår i: Sydsvenskan. - 1652-814X.
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Tidskriftsartikel (populärvet., debatt m.m.)abstract
- Det är trångt i kön till läkarutbildningen. Därför har Lunds universitet beslutat att utgå från skolbetyg vid antagning till utbildningen och att använda högskoleprovresultat som skiljekriterium vid lika meriter. Det skriver Stefan Lindgren, programdirektör, Lena Sandberg, nämndsekreterare, och Nils Danielsen, ordförande för läkarprogrammet vid Lunds universitet.
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| 44. |
- Mulder, Hindrik, et al.
(författare)
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Pituitary adenylate cyclase-activating polypeptide and islet amyloid polypeptide in primary sensory neurons : Functional implications from plasticity in expression on nerve injury and inflammation
- 1999
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Ingår i: Molecular Neurobiology. - 0893-7648. ; 19:3, s. 229-253
-
Forskningsöversikt (refereegranskat)abstract
- Primary sensory neurons serve a dual role as afferent neurons, conveying sensory information from the periphery to the central nervous system, and as efferent effectors mediating, e.g., neurogenic inflammation. Neuropeptides are crucial for both these mechanisms in primary sensory neurons. In afferent functions, they act as messengers and modulators in addition to a principal transmitter; by release from peripheral terminals, they induce an efferent response, 'neurogenic inflammation,' which comprises vasodilatation, plasma extravasation, and recruitment of immune cells. In this article, we introduce two novel members of the sensory neuropeptide family: pituitary adenylate cyclase-activating polypeptide (PACAP) and islet amyloid polypeptide (IAPP). Whereas PACAP, a vasoactive intestinal polypeptide-resembling peptide, predominantly occurs in neuronal elements, IAPP, which is structurally related to calcitonin gene-related peptide, is most widely known as a pancreatic β-cell peptide; as such, it has been recognized as a constituent of amyloid deposits in type 2 diabetes. In primary sensory neurons, under normal conditions, both peptides are predominantly expressed in small-sized nerve cell bodies, suggesting a role in nociception. On axotomy, the expression of PACAP is rapidly induced, whereas that of IAPP is reduced. Such a regulation of PACAP suggests that it serves a protective role during nerve injury, but that of IAPP may indicate that it is an excitatory messenger under normal conditions. In contrast, in localized adjuvant-induced inflammation, expression of both peptides is rapidly induced. For IAPP, studies in IAPP-deficient mice support the notion that IAPP is a pronociceptive peptide, because these mutant mice display a reduced nociceptive response when challenged with formalin.
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| 45. |
- Möller, Riitta, et al.
(författare)
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Portföljen synliggör lärandet och kompetensutvecklingen
- 2021
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Ingår i: Lakartidningen. - 0023-7205. ; 118
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Tidskriftsartikel (refereegranskat)abstract
- Portfolio used in education can be defined as a collection of documentation of performed learning activities, feedback, and progress. Currently, the documentation is electronic, hence the term e-portfolio is used. The portfolio must have a clear purpose and be aligned with the learning outcomes of the program. To be successfully implemented a portfolio must be an integral part of the education with defined tasks for both the students and the teachers. Students and teacher support in how to use the portfolio is essential especially in the beginning of the program. Learning analytics enables teachers to identify and develop support for students at risk of not achieving the outcomes.
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| 46. |
- Overgaard, Lars, et al.
(författare)
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Anti-inflammatory properties of titanium in the joint environment. An experimental study in rats
- 1998
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Ingår i: Journal of Bone and Joint Surgery: British Volume. - 2044-5377. ; 80-B:5, s. 888-893
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Tidskriftsartikel (refereegranskat)abstract
- Little is known about the tissue reactions to various implant materials which coincide with an inflammatory reaction. We used the avridine arthritis rat model to evaluate the tissue response in the synovial, interstitial and subcutaneous tissues after implant insertion. Quantitative immunohistochemistry showed that normal joint synovial tissue is dominated by ED2-positive resident macrophages. Polyethylene implants induced a much stronger foreign-body reaction than titanium implants, as measured by the number of interfacial ED1-positive macrophages. The tissue response to titanium and polyethylene was also vastly different in arthritic synovial tissue compared with control tissue. It is likely that these biomaterials interact differently with inflammatory cells or intermediary compounds. It may be that arthritic synovial tissue produces reactive oxygen intermediates (free radicals) with which titanium has a unique anti-inflammatory interaction in vitro.
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| 47. |
- Persson, Jörgen, et al.
(författare)
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Porous silicon as a neural electrode material.
- 2007
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Ingår i: Journal of Biomaterials Science. Polymer Edition. - 0920-5063. ; 18:10, s. 1301-1308
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Tidskriftsartikel (refereegranskat)abstract
- The electrical properties of the solid state/fluid (Ringer solution) interface for phosphorous- and boron-doped porous silicon are reported and the benefits of using porous silicon as neural recording electrodes are discussed. The impedance, reactance and resistance for doped porous and planar silicon, in Ringer solution, were compared to gold electrodes. Planar silicon displayed approximately a three times higher reactance than porous electrodes. The phosphorous-doped porous electrodes displayed a similar reactance compared to the gold electrodes.
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| 48. |
- Pettersson, Lina, et al.
(författare)
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Changes in expression of PACAP in rat sensory neurons in response to sciatic nerve compression.
- 2004
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Ingår i: European Journal of Neuroscience. - : Wiley. - 1460-9568 .- 0953-816X. ; 20:7, s. 1838-1848
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Tidskriftsartikel (refereegranskat)abstract
- In the present study, expression of pituitary adenylate cyclase-activating polypeptide (PACAP) in rat dorsal root ganglion (DRG) neurons and sciatic nerve following experimental sciatic nerve compression was studied with the use of quantitative immunohistochemistry and in situ hybridization. Previously, we have investigated changes in PACAP expression after nerve transection and, here, the far more frequently encountered condition of nerve compression injury is examined. Nerve compression was performed unilaterally on the rat sciatic nerve, at mid-thigh level, by application of a narrow silicone tube around the nerve for 3, 7, 14 or 28 days, respectively. We detect a statistically significant upregulation in the number and density of PACAP mRNA expression in both small and large DRG neurons in response to nerve compression. An increased number of PACAP-immunoreactive neurons is also found in the ipsilateral DRG. In addition, PACAP immunoreactivity is observed in the compressed sciatic nerve segment and adjacent nerve tissue after nerve compression. The present findings can be compared with previous studies where we have shown that PACAP expression is upregulated in DRG; in response to peripheral inflammation (primarily in small-medium neurons), and after axotomy (dramatic upregulation in medium-large neurons). In view of the recent findings of an increased PACAP expression in DRG after nerve compression, as well as the previous findings of a modulation of PACAP expression in response to axotomy and inflammation, it is likely that PACAP is also involved in the modulation of the response to peripheral nerve compression.
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| 49. |
- Pettersson, Lina, et al.
(författare)
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Expression of orphanin FQ/nociceptin and its receptor in rat peripheral ganglia and spinal cord.
- 2002
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Ingår i: Brain Research. - 1872-6240. ; 945:2, s. 266-275
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Tidskriftsartikel (refereegranskat)abstract
- Expression of the neuropeptide orphanin FQ/nociceptin (OFQ/N) and its receptor, the opioid receptor-like receptor (ORL1), have been found to have a wide distribution in the central nervous system, and in brain areas involved in sensory perception in particular. The effects of OFQ/N on, e.g., sensory transmission are very complex, and a modulatory effect on pain perception has been suggested. We therefore wanted to investigate the distribution of OFQ/N and ORL1 in the spinal cord and DRG, and also in SCG and some other peripheral tissues. The methods used were in situ hybridization, immunohistochemistry and ligand binding. We found that OFQ/N and ORL1 mRNA are expressed in DRG; primarily in small and large neurons, respectively. In spinal cord, mRNA for OFQ/N and ORL1 is expressed in neurons in laminae I, II and X, and in ventral horn neurons. Further, immunoreactivity for OFQ/N is observed in fibers and neurons in the superficial laminae of the dorsal horn and around the central canal, and also in neurons in the ventral horn of the spinal cord. Receptor ligand binding to the spinal cord grey matter is demonstrated, primarily concentrated to the dorsal horn and around the central canal, and also to medium and large size DRG neurons. These findings on the morphological distribution pattern of OFQ/N and ORL1 at the cellular level may support the notion that OFQ/N is involved in modulating pain transmission. Further, expression of OFQ/N and ORL1 mRNA was also found in SCG, whereas expression was undetectable in skin.
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| 50. |
- Pettersson, Lina M E, et al.
(författare)
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Altered behavioural responses and functional recovery in rats following sciatic nerve compression and early vs late decompression
- 2016
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Ingår i: Journal of Plastic Surgery and Hand Surgery. - 2000-656X. ; 50:6, s. 321-330
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Tidskriftsartikel (refereegranskat)abstract
- Objective: The aim of the study was to examine sensory behaviour and functional recovery in rats during nerve compression and after decompression. Compression injury is a far more common condition than nerve transection. The condition is characterised by numbness and a tingling/burning sensation, and some patients experience pain and allodynia during compression or after decompression treatment. The aetiology is in many cases unknown. Thus, further studies are of great importance for the understanding of this condition. Methods: In the present study, behavioural responses to tactile stimulation, thermal pain, as well as functional sensorimotor behaviour were investigated in rats before, during severe compression, and after decompression. The sciatic nerve of the rats was experimentally compressed for 3 or 28 days, whereafter surgical release, i.e. decompression, of the nerve was performed and the rats were examined up to ∼9 weeks. Results: An altered behaviour was found in response to compression injury, which is mitigated after early decompression treatment. Conclusions: These findings indicate that early intervention during severe compression injuries is of great importance for recovery and restoration of nerve function and, thus, should have an impact on clinical routines regarding treatment of compression injuries.
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