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  • 451.
    Höckerfelt, U
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Franzén, L
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Forsgren, S
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Substance P (NK1) receptor in relation to substance P innervation in rat duodenum after irradiation.2001In: Regulatory Peptides, ISSN 0167-0115, E-ISSN 1873-1686, Vol. 98, no 3, p. 115-26Article in journal (Refereed)
    Abstract [en]

    It has previously been shown that high dose of irradiation to the rat abdomen leads to an increased level of substance P (SP) in the duodenum. In the present study the pattern of distribution of NK1 receptors (NK1-R) in rat duodenum after irradiation (5-30 Gy), was examined at the same time-point (7 days) after irradiation, comparisons being made with the distribution of SP-innervation. Immunohistochemical methods were used. In controls, NK1-R-like immunoreactivity (-LI) was detected in epithelial cells, in cells in the region of the intestinal cells of Cajal within the deep muscular plexus (ICC-DMP), in neuronal cells in the myenteric plexus, and variably in granulocytes in the mucosa. Irradiation with 5-10 Gy did not lead to obvious changes in the pattern of NK1-R-LI. After irradiation with the highest doses (25-30 Gy), the mucosa was often gravely damaged, displaying granulation tissue. No epithelial NK1-R-LI was detected in this tissue, but was present in less affected mucosa after these doses. In the region of the ICC-DMP, in the myenteric plexus, and in granulocytes, NK1-R-LI was detected also after high dose irradiation. However, the degree of NK1-R-LI in the region of the ICC-DMP was somewhat lower than seen in controls and after low doses. SP-immunoreactive nerve fibers were present in the regions where NK1-R-LI was detected. These findings support a suggestion that an increased level of SP after irradiation may contribute to the dose-dependent gastrointestinal adverse effects that occur after radiotherapy.

  • 452.
    Höckerfelt, U
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Franzén, L
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Norrgård, O
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Forsgren, Sture
    Early increase and later decrease in VIP and substance P nerve fiber densities following abdominal radiotherapy: a study on the human colon.2002In: International Journal of Radiation Biology, ISSN 0955-3002, E-ISSN 1362-3095, Vol. 78, no 11, p. 1045-53Article in journal (Refereed)
    Abstract [en]

    PURPOSE: The neuropeptides substance P (SP) and vasoactive intestinal peptide (VIP) mediate physiologic activities in the intestine, not least in relation to motility and inflammatory processes. Neuropeptides are up-regulated and play particular importance during tissue stress. This paper aims to quantify mucosal and smooth muscle SP, VIP and total innervation in human colon in short- and long-term perspectives after abdominal irradiation.

    MATERIALS AND METHODS: Colon specimens from 23 irradiated or non-irradiated patients were investigated with immunohistochemistry and computerized image analysis. Plasma levels of SP and VIP in 15 additional patients receiving radiotherapy were analyzed.

    RESULTS: At 4-7 days after irradiation (5 x 5 Gy), the overall innervation, and also VIP and SP nerve fiber densities, were increased in both mucosa and circular muscle layer. In contrast, 5-6 weeks as well as several years after irradiation, the VIP and SP nerve fiber densities were decreased. No peptide changes were revealed in plasma.

    CONCLUSIONS: The degree of VIP and SP intestinal innervation was increased after radiotherapy in the short-term perspective but it decreased in the long-term. In the short-term, SP may have pro-inflammatory and VIP anti-inflammatory effects and the peptides may have trophic effects and be related to the occurrence of motor changes. It cannot be excluded that the decrease in VIP and SP neuronal supply seen in the long-term may contribute to intestinal malfunction.

  • 453.
    Höglund Åberg, Carola
    et al.
    Umeå University, Faculty of Medicine, Department of Odontology.
    Kelk, Peyman
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Johansson, Anders
    Umeå University, Faculty of Medicine, Department of Odontology.
    Aggregatibacter actinomycetemcomitans: virulence of its leukotoxin and association with aggressive periodontitis2015In: Virulence, ISSN 2150-5608, Vol. 6, no 3, p. 188-195Article, review/survey (Refereed)
    Abstract [en]

    Periodontitis is an infection-induced inflammatory disease that causes loss of the tooth supporting tissues. Much focus has been put on comparison of the microbial biofilm in the healthy periodontium with the diseased one. The information arising from such studies is limited due to difficulties to compare the microbial composition in these two completely different ecological niches. A few longitudinal studies have contributed with information that makes it possible to predict which individuals who might have an increased risk of developing aggressive forms of periodontitis, and the predictors are either microbial or/and host-derived factors. The most conspicuous condition that is associated with disease risk is the presence of Aggregatibacter actinomycetemcomitans at the individual level. This Gram-negative bacterium has a great genetic variation with a number of virulence factors. In this review we focus in particular on the leukotoxin that, based on resent knowledge, might be one of the most important virulence factors of A. actinomycetemcomitans.

  • 454. Ikeda, Hiroshi
    et al.
    Okazawa, Hideki
    Ohnishi, Hiroshi
    Murata, Yoji
    Oldenborg, Per-Arne
    Umeå University, Faculty of Medicine, Integrative Medical Biology, Histology and Cell Biology.
    Matozaki, Takashi
    Mutational analysis of the mechanism of negative regulation by SRC homology 2 domain-containing protein tyrosine phosphatase substrate-1 of phagocytosis in macrophages.2006In: Journal of Immunology, ISSN 0022-1767, Vol. 177, no 5, p. 3123-32Article in journal (Refereed)
    Abstract [en]

    Src homology 2 domain-containing protein tyrosine phosphatase substrate-1 (SHPS-1) is a transmembrane protein predominantly expressed in macrophages. The binding of CD47 on RBCs to SHPS-1 on macrophages is implicated in inhibition of phagocytosis of the former cells by the latter. We have now shown that forced expression in mouse RAW264.7 macrophages of a mutant version (SHPS-1-4F) of mouse SHPS-1, in which four tyrosine phosphorylation sites are replaced by phenylalanine, markedly promoted Fc gammaR-mediated phagocytosis of mouse RBCs or SRBCs. Forced expression of another mutant form (SHPS-1-deltaCyto) of mouse SHPS-1, which lacks most of the cytoplasmic region, did not promote such phagocytosis. Similarly, forced expression of a rat version of SHPS-1-4F, but not that of rat wild-type SHPS-1 or SHPS-1-deltaCyto, in RAW264.7 cells enhanced Fc gammaR-mediated phagocytosis of RBCs. Tyrosine phosphorylation of endogenous SHPS-1 as well as its association with Src homology 2 domain-containing protein tyrosine phosphatase-1 were not markedly inhibited by expression of SHPS-1-4F. Furthermore, the attachment of IgG-opsonized RBCs to RAW264.7 cells was markedly increased by expression of SHPS-1-4F, and this effect did not appear to be mediated by the interaction between CD47 and SHPS-1. These data suggest that inhibition by SHPS-1 of phagocytosis in macrophages is mediated, at least in part, in a manner independent of the transinteraction between CD47 and SHPS-1. In addition, the cytoplasmic region as well as tyrosine phosphorylation sites in this region of SHPS-1 appear indispensable for this inhibitory action of SHPS-1. Moreover, SHPS-1 may regulate the attachment of RBCs to macrophages by an as yet unidentified mechanism.

  • 455.
    Ingvarsson, Magdalena
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology.
    Höckenström, T
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Histology and Cell Biology.
    Lindgren, P
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology.
    Ridderheim, M
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Bäckström, Torbjörn
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology.
    Isolation and culture of ovarian tumour cells, cytological and cell survival evaluation1999In: Anticancer Research, ISSN 0250-7005, E-ISSN 1791-7530, Vol. 19, no 6B, p. 5069-5073Article in journal (Refereed)
    Abstract [en]

    The purpose of this study was to evaluate the reproducibility and reliability of the fluorometric microculture cytotoxicity assay (FMCA). Emphasis was placed on obtaining pure tumour cell cultures which were subjected to careful cytological evaluation. Preparations of 39 ovarian tumours, malignant, borderline and benign were made, of which 37 were successfully cultured. In 34 of the 37 tumour cell cultures, the epithelial cell fraction was > 90%, and in 30 of 39 cultures the epithelial cell fraction was > 95%. Transportation within 24 h and the 72 h incubation did not change the yield or epithelial cell fraction. There was a linear relationship between fluorescence and the number of viable cells. The fluorescence increased with time, making only comparisons within each assay plate possible. The sensitivity of the method makes it possible to perform many analyses on a small amount of material. The method also makes it possible to study cells derived from all stages of the disease, including benign tumours.

  • 456. Isa, Tadashi
    et al.
    Ohki, Yukari
    Alstermark, Bror
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Pettersson, Lars-Gunnar
    Sasaki, Shigeto
    Direct and indirect cortico-motoneuronal pathways and control of hand/arm movements.2007In: Physiology, ISSN 1548-9213, Vol. 22, p. 145-52Article in journal (Other academic)
    Abstract [en]

    Recent studies from our group have demonstrated the existence of a disynaptic excitatory cortico-motoneuronal (CM) pathway in macaque monkeys via propriospinal neurons in the midcervical segments. Results from behavioral studies with lesion of the direct pathway suggest that the indirect CM pathway can mediate the command for dexterous finger movements.

  • 457. Isa, Tadashi
    et al.
    Ohki, Yukari
    Seki, Kazuhiko
    Alstermark, Bror
    Umeå University, Faculty of Medicine, Integrative Medical Biology, Physiology.
    Properties of propriospinal neurons in the C3-C4 segments mediating disynaptic pyramidal excitation to forelimb motoneurons in the macaque monkey.2006In: Journal of Neurophysiology, ISSN 0022-3077, Vol. 95, no 6, p. 3674-85Article in journal (Refereed)
    Abstract [en]

    Candidate propriospinal neurons (PNs) that mediate disynaptic pyramidal excitation to forelimb motoneurons were studied in the C3-C4 segments in anesthetized macaque monkeys (n = 10). A total of 177 neurons were recorded (145 extracellularly, 48 intracellularly, and 16 both) in laminae VI-VII. Among these, 86 neurons (73 extracellularly, 14 intracellularly and 1 both) were antidromically activated from the forelimb motor nucleus or from the ventrolateral funiculus just lateral to the motor nucleus in the C6/C7 segments and thus are identified as PNs. Among the 73 extracellularly recorded PNs, 60 cells were fired by a train of four stimuli to the contralateral pyramid with segmental latencies of 0.8-2.2 ms, with most of them (n = 52) in a monosynaptic range (<1.4 ms including one synaptic delay and time to firing). The firing probability was only 21% from the third pyramidal volley but increased to 83% after intravenous injection of strychnine. In most of the intracellularly recorded PNs, stimulation of the contralateral pyramid evoked monosynaptic excitatory postsynaptic potentials (EPSPs, 12/14) and disynaptic inhibitory postsynaptic potentials (14/14), which were found to be glycinergic. In contrast, cells that did not project to the C6-Th1 segments where forelimb motoneurons are located were classified as segmental interneurons. These were fired from the third pyramidal volley with a probability of 71% before injection of strychnine. It is proposed that some of these interneurons mediate feed-forward inhibition to the PNs. These results suggest that the C3-C4 PNs receive feed-forward inhibition from the pyramid in addition to monosynaptic excitation and that this inhibition is stronger in the macaque monkey than in the cat. Another difference with the cat was that only 26 of the 86 PNs (30%, as compared with 84% in the cat) with projection to the forelimb motor nuclei send ascending collaterals terminating in the lateral reticular nucleus (LRN) on the ipsilateral side of the medulla. Thus we identified C3-C4 PNs that could mediate disynaptic pyramidal excitation to forelimb motoneurons in the macaque monkey. The present findings explain why it was difficult in previous studies of the macaque monkey to evoke disynaptic pyramidal excitation via C3-C4 PNs in forelimb motoneurons and why-as compared with the cat-the monosynaptic EPSPs evoked from the LRN via C3-C4 PNs were smaller in amplitude.

  • 458.
    Ishikawa-Sekigami, Tomomi
    et al.
    Gunma University.
    Kaneko, Yoriaki
    Gunma University.
    Saito, Yasuyuki
    Gunma University.
    Murata, Yoji
    Gunma University.
    Okazawa, Hideki
    Gunma University.
    Ohnishi, Hiroshi
    Gunma University.
    Oldenborg, Per-Arne
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Histology and Cell Biology.
    Nojima, Yoshihisa
    Gunma University.
    Matozaki, Takashi
    Gunma University.
    Enhanced phagocytosis of CD47-deficient red blood cells by splenic macrophages requires SHPS-1.2006In: Biochemical and Biophysical Research Communications - BBRC, ISSN 0006-291X, E-ISSN 1090-2104, Vol. 343, no 4, p. 1197-200Article in journal (Refereed)
    Abstract [en]

    The interaction of CD47 on red blood cells (RBCs) with SHPS-1 on macrophages is implicated to prevent the phagocytosis of the former cells by the latter cells. Indeed, the rate of clearance of transfused CD47-deficient (CD47(-/-)) RBCs from the bloodstream of wild-type mice was markedly increased compared with wild-type RBCs. Conversely, the rate of clearance of transfused wild-type RBCs was markedly increased in mice that expressed a mutant form of SHPS-1 lacking most of the cytoplasmic region of the protein. However, we here found that the clearance of CD47(-/-) RBCs in SHPS-1 mutant mice was minimal. In addition, the phagocytosis of CD47(-/-) RBCs by splenic macrophages from SHPS-1 mutant mice was markedly reduced compared with wild-type macrophages. These results thus suggest an additional role for CD47 on RBCs in the negative regulation of phagocytosis by macrophages and in determination of the life span of circulating RBCs.

  • 459.
    Jakobson Mo, Susanna
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Axelsson, Jan
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Jonasson, Lars
    Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Larsson, Anne
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Ögren, Mattias J.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Ögren, Margareta
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Varrone, Andrea
    Eriksson, Linda
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience.
    Bäckström, David
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    af Bjerkén, Sara
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience.
    Linder, Jan
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Riklund, Katrine
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Dopamine transporter imaging with [18F]FE-PE2I PET and [123I]FP-CIT SPECT – a clinical comparison2018In: EJNMMI Research, ISSN 2191-219X, E-ISSN 2191-219X, Vol. 8, article id 100Article in journal (Refereed)
    Abstract [en]

    Background: Dopamine transporter (DAT) imaging may be of diagnostic value in patients with clinically suspected parkinsonian disease. The purpose of this study was to compare the diagnostic performance of DAT imaging with positron emission computed tomography (PET), using the recently developed, highly DAT-selective radiopharmaceutical [18F]FE-PE2I (FE-PE2I), to the commercially available and frequently used method with [123I]FP-CIT (FP-CIT) single-photon emission computed tomography (SPECT) in early-stage idiopathic parkinsonian syndrome (PS).

    Methods: Twenty-two patients with a clinical de novo diagnosis of PS and 28 healthy controls (HC) participating in an on-going clinical trial of FE-PE2I were analyzed in this study. Within the trial protocol, participants are clinically reassessed 2 years after inclusion. A commercially available software was used for automatic calculation of FP-CIT-specific uptake ratio (SUR). MRI-based volumes of interest combined with threshold PET segmentation were used for FE-PE2I binding potential relative to non-displaceable binding (BPND) quantification and specific uptake value ratios (SUVR).

    Results: PET with FE-PE2I revealed significant differences between patients with a clinical de novo diagnosis of PS and healthy controls in striatal DAT availability (p < 0.001), with excellent accuracy of predicting dopaminergic deficit in early-stage PS. The effect sizes were calculated for FE-PE2I BPND (Glass’s Δ = 2.95), FE-PE2I SUVR (Glass’s Δ = 2.57), and FP-CIT SUR (Glass’s Δ = 2.29). The intraclass correlation (ICC) between FE-PE2I BPND FP-CIT SUR was high in the caudate (ICC = 0.923), putamen (ICC = 0.922), and striatum (ICC = 0.946), p < 0.001. Five of the 22 patients displayed preserved striatal DAT availability in the striatum with both methods. At follow-up, a non-PS clinical diagnosis was confirmed in three of these, while one was clinically diagnosed with corticobasal syndrome. In these patients, FE-PE2I binding was also normal in the substantia nigra (SN), while significantly reduced in the remaining patients. FE-PE2I measurement of the mean DAT availability in the putamen was strongly correlated with BPND in the SN (R = 0.816, p < 0.001). Olfaction and mean putamen DAT availability was correlated using both FE-PE2I BPND and FP-CIT SUR (R ≥ 0.616, p < 0.001).

    Conclusion: DAT imaging with FE-PE2I PET yields excellent basic diagnostic differentiation in early-stage PS, at least as good as FP-CIT SPECT.

  • 460.
    Janbaz, Adrihan H.
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Lindström, Mona
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Liu, Jingxia
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Pedrosa-Domellöf, Fatima
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Intermediate Filaments in the Human Extraocular Muscles2014In: Investigative Ophthalmology and Visual Science, ISSN 0146-0404, E-ISSN 1552-5783, Vol. 55, no 8, p. 5151-5159Article in journal (Refereed)
    Abstract [en]

    PURPOSE.

    To investigate the distribution of the intermediate filament (IF) proteins desmin, vimentin, and nestin in human extraocular muscles (EOMs). METHODS. Healthy adult EOM samples were serially sectioned (5 and 1 mu m) and processed for immunohistochemistry, with specific antibodies (Abs) against desmin, vimentin, and nestin and different myosin heavy chains (MyHCs), including the newly characterized Ab MYH7b against MyHC slow tonic. The distribution of desmin was also studied in EOMs at 16 to 18 weeks of gestation.

    RESULTS.

    Desmin was present in the vast majority of muscle fibers. Notably, muscle fibers that contained MyHC slow tonic were either unlabeled or very weakly labeled with three different Abs against desmin. These muscle fibers had normal cytoarchitecture and intact basement membrane. In fetal muscle, desmin was also absent or weak in myotubes containing MyHC slow tonic. Nestin was detected in a large proportion of muscle fibers in the orbital layer and to some extent also in the global layer, whereas no muscle fibers contained vimentin. Desmin and nestin were enriched at neuromuscular junctions, as in limb muscle. In contrast, some myotendinous junctions lacked desmin or nestin.

    CONCLUSIONS.

    The human EOMs differed significantly from the other muscles in the body with respect to their IF composition. Desmin, hitherto regarded as a ubiquitous muscle cytoskeletal protein, was absent or only present in trace amounts in a subset of normal muscle fibers in adult and fetal EOMs. Nestin, normally downregulated early in the postnatal period, was present in a high proportion of adult muscle fibers.

  • 461.
    Jeneskog, Torgny
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    A descending pathway to dynamic fusimotor neurones and its possible relation to a climbing fibre system1974Doctoral thesis, comprehensive summary (Other academic)
  • 462.
    Jenmalm, Per
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Birznieks, Ingvars
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Goodwin, A. W.
    Johansson, Roland S
    Influences of object shape on responses in human tactile afferents under conditions characteristic for manipulationManuscript (Other academic)
  • 463.
    Jenmalm, Per
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Schmitz, Christina
    Neuropediatric Unit, Department of Women and Child Health, Karolinska Institutet, Stockholm, Sweden / Centre National de la Recherche Scientifique–Groupe Développement et Pathologie de l’Action, Marseilles, France.
    Forssberg, Hans
    Neuropediatric Unit, Department of Women and Child Health, Karolinska Institutet, Stockholm, Sweden.
    Ehrsson, H. Henrik
    Neuropediatric Unit, Department of Women and Child Health, Karolinska Institutet, Stockholm, Sweden / Wellcome Department of Imaging Neuroscience, Institute of Neurology, London, United Kingdom.
    Lighter or heavier than predicted: neural correlates of corrective mechanisms during erroneously programmed lifts2006In: Journal of Neuroscience, ISSN 0270-6474, E-ISSN 1529-2401, Vol. 26, no 35, p. 9015-9021Article in journal (Refereed)
    Abstract [en]

    A central concept in neuroscience is that the CNS signals the sensory discrepancy between the predicted and actual sensory consequences of action. It has been proposed that the cerebellum and parietal cortex are involved in this process. A discrepancy will trigger preprogrammed corrective responses and update the engaged sensorimotor memories. Here we use functional magnetic resonance imaging with an event-related design to investigate the neuronal correlates of such discrepancies. Healthy adults repeatedly lifted an object between their right index fingers and thumbs, and on some lifting trials, the weight of the object was unpredictably changed between light (230 g) and heavy (830 g). Regardless of whether the weight was heavier or lighter than predicted, activity was found in the right inferior parietal cortex (supramarginal gyrus). This suggests that this region is involved in the comparison of the predicted and actual sensory input and the updating of the sensorimotor memories. When the object was lighter or heavier than predicted, two different types of preprogrammed force corrections occurred. There was a slow force increase when the weight of the object was heavier than predicted. This corrective response was associated with activity in the left primary motor and somatosensory cortices. The fast termination of the excessive force when the object was lighter than predicted activated the right cerebellum. These findings show how the parietal cortex, cerebellum, and motor cortex are involved in the signaling of the discrepancy between predicated and actual sensory feedback and the associated corrective mechanisms.

  • 464.
    Jergović, D
    et al.
    University of Linköping.
    Stål, Per
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Lidman, D
    University of Linköping.
    Lindvall, B
    University of Linköping.
    Hildebrand, C
    University of Linköping.
    Changes in a rat facial muscle after facial nerve injury and repair2001In: Muscle and Nerve, ISSN 0148-639X, E-ISSN 1097-4598, Vol. 24, no 9, p. 1202-1212Article in journal (Refereed)
    Abstract [en]

    This study describes changes in a rat facial muscle innervated by the mandibular and buccal facial nerve branches 4 months after nerve injury and repair. The following groups were studied: (A) normal controls; (B) spontaneous reinnervation by collateral or terminal sprouting; (C) reinnervation after surgical repair of the mandibular branch; and (D) chronic denervation. The normal muscle contained 1200 exclusively fast fibers, mainly myosin heavy chain (MyHC) IIB fibers. In group B, fiber number and fiber type proportions were normal. In group C, fiber number was subnormal. Diameters and proportions of MyHC IIA and hybrid fibers were above normal. The proportion of MyHC IIB fibers was subnormal. Immediate and delayed repair gave similar results with respect to the parameters examined. Group D rats underwent severe atrophic and degenerative changes. Hybrid fibers prevailed. These data suggest that spontaneous regeneration of the rat facial nerve is superior to regeneration after surgical repair and that immediacy does not give better results than moderate delay with respect to surgical repair. Long delays are shown to be detrimental.

  • 465.
    Jiang, Juan
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Alstermark, Bror
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Dysfunctional cortico-reticulospinal and propriospinal systems may lead to impaired skilled forelimb reaching in EphA4-knockout mice2017In: Acta Physiologica, ISSN 1748-1708, E-ISSN 1748-1716, Vol. 219, p. 34-35Article in journal (Refereed)
  • 466.
    Jiang, Juan
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Alstermark, Bror
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Not GABA But Glycine Mediates Segmental, Propriospinal, and Bulbospinal Postsynaptic Inhibition in Adult Mouse Spinal Forelimb Motor Neurons2015In: Journal of Neuroscience, ISSN 0270-6474, E-ISSN 1529-2401, Vol. 35, no 5, p. 1991-1998Article in journal (Refereed)
    Abstract [en]

    The general view is that both glycine (Eccles, 1964) and GABA (Curtis and Felix, 1971) evoke postsynaptic inhibition in spinal motor neurons. In newborn or juvenile animals, there are conflicting results showing postsynaptic inhibition in motor neurons by corelease of GABA and glycine (Jonas et al., 1998) or by glycine alone (Bhumbra et al., 2012). To resolve the relative contributions of GABA and glycine to postsynaptic inhibition, we performed in vivo intracellular recordings from forelimb motor neurons in adult mice. Postsynaptic potentials evoked from segmental, propriospinal, and bulbospinal systems in motor neurons were compared across four different conditions: control, after gabazine, gabazine followed by strychnine, and strychnine alone. No significant differences were observed in the proportion of IPSPs and EPSPs between control and gabazine conditions. In contrast, EPSPs but not IPSPs were recorded after adding strychnine with gabazine or administering strychnine alone, suggesting an exclusive role for glycine in postsynaptic inhibition. To test whether the injected (intraperitoneal) dose of gabazine blocked GABAergic inhibitory transmission, we evoked GABA(A) receptor-mediated monosynaptic IPSPs in deep cerebellar nuclei neurons by stimulation of Purkinje cell fibers. No monosynaptic IPSPs could be recorded in the presence of gabazine, showing the efficacy of gabazine treatment. Our results demonstrate that, in the intact adult mouse, the postsynaptic inhibitory effects in spinal motor neurons exerted by three different systems, intrasegmental and intersegmental as well as supraspinal, are exclusively glycinergic. These findings emphasize the importance of glycinergic postsynaptic inhibition in motor neurons and challenge the view that GABA also contributes.

  • 467.
    Jiang, Juan
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Azim, Eiman
    Ekerot, Carl-Fredrik
    Alstermark, Bror
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Direct and indirect spino-cerebellar pathways: shared ideas but different functions in motor control2015In: Frontiers in Computational Neuroscience, ISSN 1662-5188, E-ISSN 1662-5188, Vol. 9, article id 75Article in journal (Refereed)
    Abstract [en]

    The impressive precision of mammalian limb movements relies on internal feedback pathways that convey information about ongoing motor output to cerebellar circuits. The spino-cerebellar tracts (SCT) in the cervical, thoracic and lumbar spinal cord have long been considered canonical neural substrates for the conveyance of internal feedback signals. Here we consider the distinct features of an indirect spino-cerebellar route, via the brainstem lateral reticular nucleus (LRN), and the implications of this pre-cerebellar "detour" for the execution and evolution of limb motor control. Both direct and indirect spino-cerebellar pathways signal spinal interneuronal activity to the cerebellum during movements, but evidence suggests that direct SCT neurons are mainly modulated by rhythmic activity, whereas the LRN also receives information from systems active during postural adjustment, reaching and grasping. Thus, while direct and indirect spinocerebellar circuits can both be regarded as internal copy pathways, it seems likely that the direct system is principally dedicated to rhythmic motor acts like locomotion, while the indirect system also provides a means of pre-cerebellar integration relevant to the execution and coordination of dexterous limb movements.

  • 468. Jivan, Sharmila
    et al.
    Kumar, N
    Wiberg, Mikael
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy. Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Hand Surgery.
    Kay, Simon
    The influence of pre-surgical delay on functional outcome after reconstruction of brachial plexus injuries.2009In: Journal of plastic, reconstructive & aesthetic surgery : JPRAS, ISSN 1878-0539, Vol. 62, no 4, p. 472-479Article in journal (Refereed)
    Abstract [en]

    It has been proposed that delayed surgery after traumatic brachial plexus injury may adversely affect functional outcome. In this study the influence of pre-surgical delay on the outcome of brachial plexus reconstruction was examined retrospectively. All patients who underwent surgery for traumatic brachial plexus injury in the Leeds Plastic and Reconstructive Surgery unit (UK), between 1987 and 2002, were identified. Of the 110 patients identified, 27 had nerve grafting to the upper trunk to restore shoulder and biceps muscle function. Postoperative functional outcome was evaluated in this subgroup of patients. The 27 patients were divided into three groups: surgery <2 weeks (n=10), 2 weeks to 2 months (n=10) and >2 months (n=7) following injury. The efficacy of nerve grafting was correlated to pre- and postoperative biceps strength, which was assessed using the British Medical Research Council (MRC) Motor Grading Scale. In all patients the preoperative elbow grade was M0. The results showed that in the <2 weeks, 2 weeks-2 months and >2 months delay groups, the mean postoperative elbow MRC grades were 4.2+/-SD 1.0, 3.8+/-SD 0.8 and 1.1+/-SD 1.7, respectively. Functionally better results were obtained with early surgery. When surgery was delayed beyond 2 months there was no significant difference between mean pre- and postoperative elbow grades. We therefore believe that early exploration and reconstruction of adult traumatic brachial plexus injuries minimises the pernicious adverse effects of delay attributable to recent findings of the neurobiological effects of axonal damage.

  • 469. Jivan, Sharmila
    et al.
    Novikova, Liudmila N
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Wiberg, Mikael
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy. Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Hand Surgery.
    Novikov, Lev N
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    The effects of delayed nerve repair on neuronal survival and axonal regeneration after seventh cervical spinal nerve axotomy in adult rats.2006In: Experimental Brain Research, ISSN 0014-4819, E-ISSN 1432-1106, Vol. 170, no 2, p. 245-254Article in journal (Refereed)
    Abstract [en]

    It has been proposed clinically that delayed surgery after traumatic brachial plexus injury may adversely affect functional outcome. In the present experimental study the neuroprotective and growth-promoting effects of early and delayed nerve grafting following proximal seventh cervical spinal nerve (C7) axotomy were examined. The ventral branch of C7 spinal nerve was transected and axons projecting out of the proximal nerve stump were labelled with Fast Blue (FB). At the same time, the biceps brachii muscle was denervated by transecting the musculocutaneous nerve at its origin. Neuronal survival and muscle atrophy were then assessed at 1, 4, 8 and 16 weeks after permanent axotomy. In the experimental groups, a peripheral nerve graft was interposed between the transected C7 spinal nerve and the distal stump of the musculocutaneous nerve at 1 week [early nerve repair (ENR)] or 8 weeks [delayed nerve repair (DNR)] after axotomy. Sixteen weeks after nerve repair had been performed, a second tracer Fluoro-Ruby (FR) was applied distal to the graft to assess the efficacy of axonal regeneration. Counts of FB-labelled neurons revealed that axotomy did not induce any significant cell loss at 4 weeks, but 15% of motoneurons and 32% of sensory neurons died at 8 weeks after injury. At 16 weeks, the amount of cell loss in spinal cord and dorsal root ganglion (DRG) reached 29 and 50%, respectively. Both ENR and DNR prevented retrograde degeneration of spinal motoneurons and counteracted muscle atrophy, but failed to rescue sensory neurons. Due to substantial cell loss at 8 weeks, the number of FR-labelled neurons after DNR was significantly lower when compared to ENR. However, the proportion of regenerating neurons among surviving motoneurons and DRG neurons remained relatively constant indicating that neurons retained their regenerative capacity after prolonged axotomy. The results demonstrate that DNR could protect spinal motoneurons and reduce muscle atrophy, but had little effect on sensory DRG neurons. However, the efficacy of neuroprotection and axonal regeneration will be significantly affected by the amount of cell loss already presented at the time of nerve repair.

  • 470.
    Johansson, Amanda
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Forsgren, Sture
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Stenberg, Berndt
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Dermatology and Venerology.
    Wilén, Jonna
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Kalezic, Nebojsa
    Sandström, Monica
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    No effect of mobile phone-like RF exposure on patients with atopic dermatitis.2008In: Bioelectromagnetics, ISSN 1521-186X, Vol. 29, no 5, p. 353-362Article in journal (Refereed)
    Abstract [en]

    This study investigates the effect of exposure to a mobile phone-like radiofrequency (RF) electromagnetic field on people with atopic dermatitis (AD). Fifteen subjects with AD were recruited and matched with 15 controls without AD. The subjects were exposed for 30 min to an RF field at 1 W/kg via an indoor base station antenna attached to a 900 MHz GSM mobile phone. Blood samples for ELISA analysis of the concentration of substance P (SP), tumor necrosis factor receptor 1 (TNF R1), and brain derived neurotrophic factor (BDNF) in serum were drawn before and after the provocation (exposure/sham). Baseline heart rate and heart rate variability, local blood flow, and electrodermal activity were also recorded. No significant differences between the subject groups were found for baseline neurophysiological data. The cases displayed a serum concentration of TNF R1 significantly higher than the control subjects and a significantly lower serum concentration of BDNF in the baseline condition. For SP there was no difference between groups. However, no effects related to RF exposure condition were encountered for any of the measured substances. As to symptoms, a possible correlation with exposure could not be evaluated, due to too few symptom reports. The result of the study does not support the hypothesis of an effect of mobile phone-like RF exposure on serum levels of SP, TNF R1, and BDNF in persons with AD.

  • 471.
    Johansson, Anders
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Context dependent adaptation of biting behavior in human2014Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The focus of this thesis was to study an action that humans perform regularly, namely, to hold a morsel between the teeth and split it into smaller pieces. Three different issues related to this biting behavior were addressed:  (1) the effect of redu­c­ed perio­dontal tissues on food holding and splitting behavior; (2) the behavioral conse­quences of performing different bite tasks with different functional requirements, i.e., to split a peanut half resting on a piece of chocolate or to split both the peanut and the chocolate; and (3) the reflex modulations resul­ting from such a change in the intended bite action. The main conclusions from the experi­mental studies were the following:

    First, perio­dontitis, an inflam­matory disease that destroys the peri­o­dontal ligaments and the embedded perio­dontal mechanoreceptors, causes significant impairments in the masticatory abili­ty: the manipulative bite forces when holding a morsel are elevated compared to a matched control population and the bite force development prior to food split is altered. These changes are likely due to a combination of reduced sensory informa­tion from the damaged ligaments and to changes in the bite stra­tegy secon­d­ary to the unstable oral situation.

    Second, people exploit the anatomy of jaw-closing muscles to regulate the amount of bite force that dissipates following a sudden unloading of the jaw. Such control is necessary because without mechanisms that quickly halt jaw-closing movements after sudden unloading, the impact forces when the teeth collide could otherwise damage both the teeth and related soft tissues. Splitting a piece of chocolate, for instance, regularly requires >100N of bite force and the jaws collide within 5 ms of a split. On the other hand, when biting through heterogeneous food, the bite force needs to be kept high until the whole morsel is split. The required regulation is achieved by differen­tial­ly engaging parts of the masseter muscles along the anteroposterior axis of the jaw to exploit differences between muscle portions in their bite force generating capa­ci­ty and muscle shortening velocity.

    Finally, the reflex evoked by suddenly unloading the jaw—apparent only after the initial bite force dissipation—is modulated according to the bite intention. That is, when the intention is to bite through food items with multiple layers, the reflex response in the jaw opening muscles following a split is small, thus minimizing the bite force reduction. In contrast, when the intention is to rapidly decrease the bite force once a split has occurred, the reflex response is high. This pattern of reflex modulation is functionally beneficial when biting through heterogeneous food in a smooth manner.

    The presented studies show the significance of integrating cogni­tive, physiological and anatomical aspects when attempting to understand human masticatory control.

  • 472.
    Johansson, Anders Sixten
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Pruszynski, J Andrew
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Edin, Benoni Benjamin
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Westberg, Karl-Gunnar
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Biting intentions modulate digastric reflex responses to sudden unloading of the jaw2014In: Journal of Neurophysiology, ISSN 0022-3077, E-ISSN 1522-1598, Vol. 112, no 5, p. 1067-1073Article in journal (Refereed)
    Abstract [en]

    Reflex responses in jaw opening muscles can be evoked when a brittle object cracks between the teeth and suddenly unloads the jaw. We hypothesized that this reflex response is flexible and, as such, is modulated according to the instructed goal of biting through an object. Study participants performed two different biting tasks when holding a peanut-half stacked on a chocolate piece between their incisors. In one task, they were asked to split the peanut-half only (single-split task) and, in the other task, they were asked to split both the peanut and the chocolate in one action (double-split task). In both tasks, the peanut split evoked a jaw opening muscle response, quantified from EMG recordings of the digastric muscle in a window 20-60 ms following peanut split. Consistent with our hypothesis, we found that the jaw opening muscle response in the single-split trials was about twice the size of the jaw opening muscle response in the double-split trials. A linear model that predicted the jaw opening muscle response on a single trial basis indicated that task settings played a significant role in this modulation but also that the pre-split digastric muscle activity contributed to the modulation. These findings demonstrate that, like reflex responses to mechanical perturbations in limb muscles, reflex responses in jaw muscles not only show gain-scaling but also are modulated by subject intent.

  • 473.
    Johansson, Anders
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Westberg, Karl-Gunnar
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Edin, Benoni B.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Task-dependent control of the jaw during food splitting in humans2014In: Journal of Neurophysiology, ISSN 0022-3077, E-ISSN 1522-1598, Vol. 111, p. 2614-2623Article in journal (Refereed)
    Abstract [en]

    Although splitting of food items between the incisors often requires high bite forces, rarely do the teeth harmfully collide when the jaw quickly closes after split. Previous studies indicate that the force-velocity relationship of the jaw closing muscles principally explains the prompt dissipation of jaw closing force. Here, we asked whether people could regulate the dissipation of jaw closing force during food splitting. We hypothesized that such regulation might be implemented via differential recruitment of masseter muscle portions situated along the anteroposterior axis because these portions will experience a different shortening velocity during jaw closure. Study participants performed two different tasks when holding a peanut-half stacked on a chocolate piece between their incisors. In one task, they were asked to split the peanut-half only (single-split trials) and, in the other, to split both the peanut and the chocolate in one action (double-split trials). In double-split trials following the peanut split, the intensity of the tooth impact on the chocolate piece was on average 2.5 times greater than in single-split trials, indicating a substantially greater loss of jaw closing force in the single-split trials. We conclude that control of jaw closing force dissipation following food splitting depends on task demands. Consistent with our hypothesis, converging neurophysiological and morphometric data indicated that this control involved a differential activation of the jaw closing masseter muscle along the anteroposterior axis. These latter findings suggest that the regulation of jaw closing force after sudden unloading of the jaw exploits masseter muscle compartmentalization.

  • 474.
    Johansson, B
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Eriksson, A
    Ramaekers, F
    Thornell, L
    Smoothelin in adult and developing human arteries and myocardium.1999In: Histochemistry and Cell Biology, ISSN 0948-6143, E-ISSN 1432-119X, Vol. 112, no 4, p. 291-9Article in journal (Refereed)
    Abstract [en]

    The aim of this investigation was to study, with immunohistochemical methods, the distribution of the novel cytoskeletal protein smoothelin in human cardiovascular tissues, the possible changes during the development of the cardiovascular system and its correlation to the intermediate filament proteins desmin and vimentin. Smoothelin was detected in smooth muscle cells of the fetal coronary arteries. In very young subjects (up to 3 months of age), only a few cells in the media of the elastic arteries contained smoothelin, whereas it was present in most smooth muscle cells in the muscular arteries. In individuals older than 1 year, most smooth muscle cells in the media of all blood vessels contained smoothelin. In vessels with a developed intima, smoothelin was present in a variable proportion of the smooth muscle cells. With few exceptions, smoothelin was more frequently detected than desmin in medial smooth muscle cells. Smoothelin and vimentin were codistributed in the smooth muscle cells of the media in most vessels. In the cardiomyocytes (fetal to adult age), the smoothelin antibody detected epitopes located at the Z-disc level but not in the intercalated discs. In conclusion, smoothelin is more widely distributed in the muscular arteries than in the elastic arteries early in life, and thus exhibits a variable distribution during postnatal development of vascular tissues. In the adult, smoothelin is detected in the media of most vascular smooth muscle cells, both in muscular and elastic arteries, and is not necessarily codistributed with either desmin or vimentin. Evidence that smoothelin is present in human striated cardiomyocytes is also presented.

  • 475.
    Johansson, B
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Eriksson, A
    Virtanen, I
    Thornell, L E
    Intermediate filament proteins in adult human arteries.1997In: Anatomical Record, ISSN 0003-276X, E-ISSN 1097-0185, Vol. 247, no 4, p. 439-48Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The cytoskeleton of cells in blood vessel walls contains desmin, vimentin, and cytokeratins. The distribution of these proteins in human vessels is not fully known. We have mapped the distribution of intermediate filament proteins in human arterial walls.

    METHODS: Monoclonal antibodies targeted at the intermediate filament proteins desmin, vimentin, and cytokeratins were used, and the distribution of these proteins was studied by immunohistochemistry.

    RESULTS: In the muscular arteries, most smooth muscle cells in the media expressed both desmin and vimentin; in the elastic arteries, the proportion of desmin-labelled cells was lower and preferentially located to the periphery of the media. In general, the desmin immunoreactivity within the intima was weak, but some smooth muscle cells and smooth muscle cells in the musculoelastic layer showed strong immunoreactivity. The vasa vasorum exhibited a heterogeneous desmin-labelling pattern. The vimentin antibodies labelled the endothelium and showed a heterogeneous staining pattern in the other layers of the arterial wall. Cytokeratin was detected in occasional cells in the media of muscular arteries, in many adluminal cells and cell clusters in the coronary intima, and in smooth muscle cells in the media of the elastic arteries.

    CONCLUSIONS: Vimentin is widely distributed in vascular smooth muscle cells, whereas the distribution of desmin and cytokeratin varies. Each artery studied had an intermediate filament pattern typical for the anatomical location. There were no interindividual variations in the distribution of intermediate filament proteins.

  • 476.
    Johansson, Bengt
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine. Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Mörner, Stellan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Waldenström, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Stål, Per
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Myocardial capillary supply is limited in hypertrophic cardiomyopathy: a morphological analysis2008In: International Journal of Cardiology, ISSN 0167-5273, E-ISSN 1874-1754, Vol. 126, no 2, p. 252-257Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To clarify the morphological basis of the limited coronary reserve in hypertrophic cardiomyopathy (HCM). BACKGROUND: Some of the symptoms in Hypertrophic cardiomyopathy (HCM), such as chest pain, dyspnea and arrhythmia, may be explained by myocardial ischemia. Many patients with HCM are known to exhibit these symptoms in the absence of atherosclerosis in the major coronary vessels. Decreased myocardial perfusion has been demonstrated in HCM, however, little is known about the myocardial capillary morphology in this disease. METHODS: Using immunohistochemistry and morphometry, we analysed capillaries and cardiomyocytes in myectomy specimens from 5 patients with HCM with moderate hypertrophy and left ventricular outflow tract obstruction and in 5 control hearts. RESULTS: The number of capillaries per cardiomyocyte (p<0.009) and number of capillaries per cardiomyocyte area unit, reflecting cardiomyocyte mass (p=0.009), were lower in individuals with HCM, i.e. indicating loss of capillaries. In HCM, the capillary density was 33% lower (p<0.05). CONCLUSIONS: Our morphologic findings show that the capillary supply, and thus the coronary reserve, is impaired in HCM with moderate hypertrophy and left ventricular outflow tract obstruction. These data may partly explain the limitation of myocardial perfusion in HCM, which is associated with worse prognosis. Furthermore, we present evidence of actual loss of myocardial capillaries in HCM and a defective capillary growth.

  • 477.
    Johansson, Cecilia
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Jonsson, Mari
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Marttila, Marko
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Persson, David
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Fan, Xiao-Long
    Skog, Johan
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Frängsmyr, Lars
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Sports Medicine. Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Wadell, Göran
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Arnberg, Niklas
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Adenoviruses use lactoferrin as a bridge for CAR-independent binding to and infection of epithelial cells2007In: Journal of Virology, ISSN 0022-538X, E-ISSN 1098-5514, Vol. 81, no 2, p. 954-963Article in journal (Refereed)
    Abstract [en]

    Most adenoviruses bind to the coxsackie- and adenovirus receptor (CAR). Surprisingly, CAR is not expressed apically on polarized cells and is thus not easily available to viruses. Consequently, alternative mechanisms for entry of coxsackievirus and adenovirus into cells have been suggested. We have found that tear fluid promotes adenovirus infection, and we have identified human lactoferrin (HLf) as the tear fluid component responsible for this effect. HLf alone was found to promote binding of adenovirus to epithelial cells in a dose-dependent manner and also infection of epithelial cells by adenovirus. HLf was also found to promote gene delivery from an adenovirus-based vector. The mechanism takes place at the binding stage and functions independently of CAR. Thus, we have identified a novel binding mechanism whereby adenovirus hijacks HLf, a component of the innate immune system, and uses it as a bridge for attachment to host cells.

  • 478.
    Johansson, Eva
    et al.
    Umeå University, Faculty of Medicine, Public Health and Clinical Medicine, Family Medicine.
    Hamberg, Katarina
    Umeå University, Faculty of Medicine, Integrative Medical Biology. Umeå University, Faculty of Medicine, Public Health and Clinical Medicine, Family Medicine.
    Lindgren, Gerd
    Westman, Göran
    Umeå University, Faculty of Medicine, Public Health and Clinical Medicine, Family Medicine.
    "How could I even think of a job?"--Ambiguities in working life in a group of female patients with undefined musculoskeletal pain.1997In: Scand J Prim Health Care, ISSN 0281-3432, Vol. 15, no 4, p. 169-74Article in journal (Refereed)
  • 479.
    Johansson, Johanna
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Histology and Cell Biology. Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics. Masterprogrammet i biomedicin.
    The cell-surface flycoprotein CD47 regulates apoptosis in murine neutrophils2014Independent thesis Advanced level (degree of Master (Two Years)), 30 credits / 45 HE creditsStudent thesis
  • 480.
    Johansson, Jonas
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Sustainable Health. Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Geriatric Medicine.
    Jarocka, Ewa
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Westling, Göran
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Nordström, Anna
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Sustainable Health.
    Nordström, Peter
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Geriatric Medicine.
    Predicting incident falls: Relationship between postural sway and limits of stability in older adults2019In: Human Movement Science, ISSN 0167-9457, E-ISSN 1872-7646, Vol. 66, p. 117-123Article in journal (Refereed)
    Abstract [en]

    Background We have previously shown that objective measurements of postural sway predicts fall risk, although it is currently unknown how limits of stability (LOS) might influence these results.

    Research question: How integrated postural sway and LOS measurements predict the risk of incident falls in a population-based sample of older adults.

    Methods: The sample for this prospective observational study was drawn from the Healthy Ageing Initiative cohort and included data collected between June 2012 and December 2016 for 2396 men and women, all 70 years of age. LOS was compared to postural sway with measurements during eyes-open (EO) and eyes-closed (EC) trials, using the previously validated Wii Force Plate. Fall history was assessed during baseline examination and incident falls were collected during follow-up at 6 and 12 months. Independent predictors of incident falls and additional covariates were investigated using multiple logistic regression models.

    Results: During follow-up, 337 out of 2396 participants (14%) had experienced a fall. Unadjusted regression models from the EO trial revealed increased fall risk by 6% (OR 1.06, 95% CI 1.02–1.11) per each centimeter squared increase in sway area and by 16% (OR 1.16, 95% CI 1.07–1.25) per 1-unit increase in Sway-Area-to-LOS ratio. Odds ratios were generally lower when analyzing EC trials and only slightly attenuated in fully adjusted models.

    Significance: Integrating postural sway and LOS parameters provides valid fall risk prediction and a holistic analysis of postural stability. Future work should establish normative values and evaluate clinical utility of these measures.

  • 481.
    Johansson, Jonas
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine. Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Geriatric Medicine.
    Nordström, Anna
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Gustafson, Yngve
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Geriatric Medicine.
    Westling, Göran
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Nordström, Peter
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Geriatric Medicine.
    Increased postural sway during quiet stance as a risk factor for prospective falls in community-dwelling elderly individuals2017In: Age and Ageing, ISSN 0002-0729, E-ISSN 1468-2834, Vol. 46, no 6, p. 964-970Article in journal (Refereed)
    Abstract [en]

    Objective: fall-related injuries constitute major health risks in older individuals, and these risks are projected to increase in parallel with increasing human longevity. Impaired postural stability is a potential risk factor related to falls, although the evidence is inconclusive, partly due to the lack of prospective studies. This study aimed to investigate how objective measures of postural sway predict incident falls.

    Design, setting and participants: this prospectively observational study included 1,877 community-dwelling individuals aged 70 years who participated in the Healthy Ageing Initiative between June 2012 and December 2015.

    Measurements: postural sway was measured during eyes-open (EO) and eyes-closed (EC) trials using the Wii Balance Board. Functional mobility, muscle strength, objective physical activity and cognitive performance were also measured. Participants reported incident falls 6 and 12 months after the examination.

    Results: during follow-up, 255 (14%) prospective fallers were identified. Division of centre of pressure (COP) sway lengths into quintiles revealed a nonlinear distribution of falls for EO trial data, but not EC trial data. After adjustment for multiple confounders, fall risk was increased by 75% for participants with COP sway lengths ≥400 mm during the EO trial (odds ratio [OR] 1.75, 95% confidence interval [CI] 1.09-2.79), and approximately doubled for sway lengths ≥920 mm during the EC trial (OR 1.90, 95% CI 1.12-3.22).

    Conclusion: objective measures of postural sway independently predict incident falls in older community-dwelling men and women. Further studies are needed to evaluate whether postural sway length is of interest for the prediction of incident falls in clinical settings.

  • 482.
    Johansson, Malin
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Jönsson, Maria
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Norrgård, Orjan
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Forsgren, Sture
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    New aspects concerning ulcerative colitis and colonic carcinoma: analysis of levels of neuropeptides, neurotrophins, and TNFalpha/TNF receptor in plasma and mucosa in parallel with histological evaluation of the intestine2008In: Inflammatory Bowel Diseases, ISSN 1078-0998, E-ISSN 1536-4844, Vol. 14, no 10, p. 1331-1340Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The levels of neuropeptides, neurotrophins, and TNFalpha (TNFalpha)/TNF receptor in plasma and mucosa for patients with ulcerative colitis (UC) and colonic carcinoma, and concerning plasma also for healthy controls, were examined. Moreover, the relationships between the different substances and the influence of mucosal derangement on the levels were analyzed.

    METHODS: The levels of VIP, SP, CGRP, BDNF, NGF, and TNFalpha/TNF receptor 1 were measured using ELISA/EIA.

    RESULTS: Patients with UC demonstrated the highest levels of all analyzed substances in plasma, with the exception of BDNF. However, there were differences within the UC group, patients treated with corticosteroids, and/or nonsteroid antiinflammatory/immunosuppressive treatment having higher plasma levels than those not given these treatments. Patients with colonic carcinoma showed higher SP and TNF receptor 1 levels in plasma compared to healthy controls. Concerning mucosa, the levels of almost all analyzed substances were elevated for patients with UC compared to noncancerous mucosa of colonic carcinoma patients. There were correlations between many of the substances in both plasma and mucosa, especially concerning the 3 neuropeptides examined. There were also marked associations with mucosa derangement.

    CONCLUSIONS: Via analysis of correlations for the respective patients and via comparisons between the different patient groups, new and original information was obtained. Interestingly, the degree of mucosal affection was markedly correlated with tissue levels of the substances and the treatments were found to be of importance concerning plasma but not tissue levels of these. Combined plasma analysis of neuropeptides, neurotrophins, and TNF receptor 1 may help to distinguish UC and colonic carcinoma patients.

  • 483.
    Johansson, Malin
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Norrgård, Örjan
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Forsgren, Sture
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Are neurotrophins important in ulcerative colitis?2007In: Annals of the New York Academy of Sciences, ISSN 0077-8923, E-ISSN 1749-6632, Vol. 1107, p. 290-299Article in journal (Other academic)
    Abstract [en]

    Neurotrophins are known to have growth, survival-promoting, and healing effects. The importance of neurotrophins in ulcerative colitis (UC) is, however, unclear. Recent studies in our group revealed that an occurrence of marked changes in neurotrophin expression patterns was related to a worsening of the disease process. There was thus an upregulation for the lamina propria cells but a downregulation in nerve structures concerning neurotrophin expressions in severe UC. The observations show that changes in the neurotrophin system are a part of the disease process in UC and are of interest as treatments interfering with neurotrophin effects in other situations have been found to have trophic and healing effects.

  • 484.
    Johansson, Malin
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Norrgård, Örjan
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences.
    Forsgren, Sture
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Study of expression patterns and levels of neurotrophins and neurotrophin receptors in ulcerative colitis2007In: Inflammatory Bowel Diseases, ISSN 1078-0998, E-ISSN 1536-4844, Vol. 13, no 4, p. 398-409Article in journal (Refereed)
    Abstract [en]

    Background: Neurotrophins may be involved in ulcerative colitis (UC). Yet, it is unclear whether if their effects should be blocked.

    Methods: In this study, the neurotrophins nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) and their receptors were examined by immunohistochemistry, ELISA, and RT-PCR.

    Results: BDNF immunoreaction was detected in nerve structures in particular, and NGF immunoreaction was detected in lamina propria cells. Cellular NGF immunoreaction was generally observed to be higher in the mucosa of UC patients than in the controls. In addition, UC patients demonstrated significantly higher p75 immunoreaction (P = 0.010) in lamina propria cells. The controls expressed significantly higher BDNF immunoreaction in the nerve structures than did UC patients (P = 0.000). However, the UC group showed marked interindividual variation in expression of neurotrophins and neurotrophin receptors. This included variation at the mRNA level for NGF. Differences with the controls were most pronounced in UC specimens demonstrating great infiltration of inflammatory cells and marked tissue derangement. Corticosteroid treatment seemed to affect neurotrophin production in lamina propria cells but not in nerve structures. These observations demonstrate that up-regulation and down-regulation of neurotrophins occur in different structural components in response to the disease process. Massive inflammation seemed to be correlated with decreased neurotrophin immunoreaction in nerve structures, but there was a tendency toward increased neurotrophin production in lamina propria cells.

    Conclusions: Our study shows that UC patients are not a uniform group in their expression of neurotrophins, a fact that should be considered when discussing therapeutic interventions.

  • 485.
    Johansson, R S
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Westling, G
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Bäckström, A
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Flanagan, J R
    Queen's University, Kingston, Canada.
    Eye-hand coordination in object manipulation.2001In: Journal of Neuroscience, ISSN 0270-6474, E-ISSN 1529-2401, Vol. 21, no 17, p. 6917-32Article in journal (Refereed)
    Abstract [en]

    We analyzed the coordination between gaze behavior, fingertip movements, and movements of the manipulated object when subjects reached for and grasped a bar and moved it to press a target-switch. Subjects almost exclusively fixated certain landmarks critical for the control of the task. Landmarks at which contact events took place were obligatory gaze targets. These included the grasp site on the bar, the target, and the support surface where the bar was returned after target contact. Any obstacle in the direct movement path and the tip of the bar were optional landmarks. Subjects never fixated the hand or the moving bar. Gaze and hand/bar movements were linked concerning landmarks, with gaze leading. The instant that gaze exited a given landmark coincided with a kinematic event at that landmark in a manner suggesting that subjects monitored critical kinematic events for phasic verification of task progress and subgoal completion. For both the obstacle and target, subjects directed saccades and fixations to sites that were offset from the physical extension of the objects. Fixations related to an obstacle appeared to specify a location around which the extending tip of the bar should travel. We conclude that gaze supports hand movement planning by marking key positions to which the fingertips or grasped object are subsequently directed. The salience of gaze targets arises from the functional sensorimotor requirements of the task. We further suggest that gaze control contributes to the development and maintenance of sensorimotor correlation matrices that support predictive motor control in manipulation.

  • 486.
    Johansson, Roland
    et al.
    Umeå University, Faculty of Medicine, Integrative Medical Biology, Physiology.
    Birznieks, Ingvars
    Umeå University, Faculty of Medicine, Integrative Medical Biology, Physiology.
    First spikes in ensembles of human tactile afferents code complex spatial fingertip events.2004In: Nature Neuroscience, ISSN 1097-6256, Vol. 7, no 2, p. 170-7Article in journal (Refereed)
    Abstract [en]

    It is generally assumed that primary sensory neurons transmit information by their firing rates. However, during natural object manipulations, tactile information from the fingertips is used faster than can be readily explained by rate codes. Here we show that the relative timing of the first impulses elicited in individual units of ensembles of afferents reliably conveys information about the direction of fingertip force and the shape of the surface contacting the fingertip. The sequence in which different afferents initially discharge in response to mechanical fingertip events provides information about these events faster than the fastest possible rate code and fast enough to account for the use of tactile signals in natural manipulation.

  • 487.
    Johansson, Roland
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Flanagan, JR
    Queen’s University, Kingston, ON, Canada.
    Tactile sensory control of object manipulation in humans2008In: The senses, a comprehensive reference: somatotsensation Vol 6 / [ed] Esther Gardner, Jon H Kaas, Amsterdam: Elsevier , 2008, 1, Vol. 6, p. 67-86Chapter in book (Other (popular science, discussion, etc.))
    Abstract [en]

    Dexterous object manipulation is a hallmark of human skill. The versatility of the human hands in manipulation tasks depends on both the anatomical structure of the hands and the neural machinery that controls them. Research during the last 20 years has led to important advances in our understanding of the sensorimotor control mechanisms that underlie dexterous object manipulation. This article focuses on the sensorimotor control of fingertip actions with special emphasis on the role of tactile sensory mechanisms. It highlights the importance of sensory predictions, especially related to mechanical contact events around which manipulation tasks are organized, and analyzes how such predictions are influenced by tactile afferent signals recorded in single neurons in awake humans.

  • 488.
    Johansson, Roland S
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Dynamic use of tactile afferent signals in control of dexterous manipulation.2002In: Advances in Experimental Medicine and Biology, ISSN 0065-2598, E-ISSN 2214-8019, Vol. 508, p. 397-410Article in journal (Refereed)
    Abstract [en]

    During object manipulation, humans select and activate neural action programs acquired during ontogenetic development. A basic issue in understanding the control of dexterous manipulation is to learn how people use sensory information to adapt the output of these neural programs such that the fingertip actions matches the requirements imposed by the physical properties of the manipulated object, e.g., weight (mass), slipperiness, shape, and mass distribution. Although visually based identification processes contribute to predictions of required fingertip actions, the digital tactile sensors provide critical information for the control of fingertip forces. The present account deals with the tactile afferent signals from the digits during manipulation and focuses on some specific issues that the neural controller has to deal with to make use of tactile information.

  • 489.
    Johansson, Roland S
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Nervceller i samarbete2008In: Det friska och det sjuka nervsystemet, Umeå: Medicinska fakulteten , 2008Chapter in book (Other (popular science, discussion, etc.))
  • 490.
    Johansson, Roland S
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Flanagan, J Randall
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Coding and use of tactile signals from the fingertips in object manipulation tasks2009In: Nature Reviews Neuroscience, ISSN 1471-003X, E-ISSN 1471-0048, Vol. 10, no 5, p. 345-359Article in journal (Refereed)
    Abstract [en]

    During object manipulation tasks, the brain selects and implements action-phase controllers that use sensory predictions and afferent signals to tailor motor output to the physical properties of the objects involved. Analysis of signals in tactile afferent neurons and central processes in humans reveals how contact events are encoded and used to monitor and update task performance.

  • 491.
    Johansson, Roland S
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Flanagan, J Randall
    Umeå University, Faculty of Medicine, Department of Odontology.
    Sensorimotor control of manipulation2009In: Encyclopedia of Neuroscience, Elsevier , 2009, 8, p. 593-604Chapter in book (Other (popular science, discussion, etc.))
  • 492.
    Johansson, Roland S
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Flanagan, JR
    Sensory control of object manipulation2009In: Sensorimotor control of grasping: Physiology and pathophysiology / [ed] Dennis A. Nowak, Joachim Hermsdörfer., Cambridge: Cambridge books , 2009, p. 141-160Chapter in book (Other (popular science, discussion, etc.))
    Abstract [en]

    Series of action phases characterize natural object manipulation tasks where each phase is responsible for satisfying a task subgoal. Subgoal attainment typically corresponds to distinct mechanical contact events, either involving the making or breaking of contact between the digits and an object or between a held object and another object. Subgoals are realized by the brain selecting and sequentially implementing suitable action-phase controllers that use sensory predictions and afferents signals in specific ways to tailor the motor output in anticipation of requirements imposed by objects' physical properties. This chapter discusses the use of tactile and visual sensory information in this context. It highlights the importance of sensory predictions, especially related to the discrete and distinct sensory events associated with contact events linked to subgoal completion, and considers how sensory signals influence and interact with such predictions in the control of manipulation tasks.

  • 493.
    Johansson, Roland S
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Häger, Charlotte
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Riso, Ronald
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Somatosensory control of precision grip during unpredictable pulling loads. II. Changes in load force rate.1992In: Experimental Brain Research, ISSN 0014-4819, E-ISSN 1432-1106, Vol. 89, no 1, p. 192-203Article in journal (Refereed)
    Abstract [en]

    In the previous paper regarding the somatosensory control of the human precision grip, we concluded that the elicited automatic grip force adjustments are graded by the amplitude of the imposed loads when restraining an 'active' object subjected to unpredictable pulling forces (Johansson et al. 1992a). Using the same subjects and apparatus, the present study examines the capacity to respond to imposed load forces applied at various rates. Grip and load forces (forces normal and tangential to the grip surfaces) and the position of the object in the pulling direction (distal) were recorded. Trapezoidal load force profiles with plateau amplitudes of 2 N were delivered at the following rates of loading and unloading in an unpredictable sequence: 2 N/s, 4 N/s or 8 N/s. In addition, trials with higher load rate (32 N/s) at a low amplitude (0.7 N) were intermingled. The latencies between the start of the loading and the onset of the grip force response increased with decreasing load force rate. They were 80 +/- 9 ms, 108 +/- 13 ms, 138 +/- 27 ms and 174 +/- 39 ms for the 32, 8, 4 and 2 N/s rates, respectively. These data suggested that the grip response was elicited after a given minimum latency once a load amplitude threshold was exceeded. The amplitude of the initial rapid increase of grip force (i.e., the 'catch-up' response) was scaled by the rate of the load force, whereas its time course was similar for all load rates. This response was thus elicited as a unit, but its amplitude was graded by afferent information about the load rate arising very early during the loading. The scaling of the catch-up response was purposeful since it facilitated a rapid reconciliation of the ratio between the grip and load force to prevent slips. In that sense it apparently also compensated for the varying delays between the loading phase and the resultant grip force responses. However, modification of the catch-up response may occur during its course when the loading rate is altered prior to the grip force response or very early during the catch-up response itself. Hence, afferent information may be utilized continuously in updating the response although its motor expression may be confined to certain time contingencies. Moreover, this updating may take place after an extremely short latency (45-50 ms).

  • 494.
    Johansson, Roland S
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Riso, Ronald
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Häger, Charlotte
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Bäckström, Lars
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Somatosensory control of precision grip during unpredictable pulling loads. I. Changes in load force amplitude.1992In: Experimental Brain Research, ISSN 0014-4819, E-ISSN 1432-1106, Vol. 89, no 1, p. 181-191Article in journal (Refereed)
    Abstract [en]

    In manipulating 'passive' objects, for which the physical properties are stable and therefore predictable, information essential for the adaptation of the motor output to the properties of the current object is principally based on 'anticipatory parameter control' using sensorimotor memories, i.e., an internal representation of the object's properties based on previous manipulative experiences. Somatosensory afferent signals only intervene intermittently according to an 'event driven' control policy. The present study is the first in a series concerning the control of precision grip when manipulating 'active' objects that exert unpredictable forces which cannot be adequately represented in a sensorimotor memory. Consequently, the manipulation may be more reliant on a moment-to-moment sensory control. Subjects who were prevented from seeing the hand used the precision grip to restrain a manipulandum with two parallel grip surfaces attached to a force motor which produced distally directed (pulling) loads tangential to the finger tips. The trapezoidal load profiles consisted of a loading phase (4 N/s), plateau phase and an unloading phase (4 N/s) returning the load force to zero. Three force amplitudes were delivered in an unpredictable sequence; 1 N, 2 N and 4 N. In addition, trials with higher load rate (32 N/s) at a low amplitude (0.7 N), were superimposed on various background loads. The movement of the manipulandum, the load forces and grip forces (normal to the grip surfaces) were recorded at each finger. The grip force automatically changed with the load force during the loading and unloading phases. However, the grip responses were initiated after a brief delay. The response to the loading phase was characterized by an initial fast force increase termed the 'catch-up' response, which apparently compensated for the response delay--the grip force adequately matched the current load demands by the end of the catch-up response. In ramps with longer lasting loading phases (amplitude greater than or equal to 2 N) the catch-up response was followed by a 'tracking' response, during which the grip force increased in parallel with load force and maintained an approximately constant force ratio that prevented frictional slips. The grip force during the hold phase was linearly related to the load force, with an intercept close to the grip force used prior to the loading. Likewise, the grip force responses evoked by the fast loadings superimposed on existing loads followed the same linear relationship.(ABSTRACT TRUNCATED AT 400 WORDS)

  • 495.
    Johansson, Roland
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Theorin, Anna
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Westling, Göran
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Andersson, Micael
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Ohki, Yukari
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Nyberg, Lars
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    How a lateralized brain supports symmetrical bimanual tasks2006In: PLoS biology, ISSN 1544-9173, E-ISSN 1545-7885, Vol. 4, no 6, p. e158-Article in journal (Refereed)
    Abstract [en]

    A large repertoire of natural object manipulation tasks require precisely coupled symmetrical opposing forces by both hands on a single object. We asked how the lateralized brain handles this basic problem of spatial and temporal coordination. We show that the brain consistently appoints one of the hands as prime actor while the other assists, but the choice of acting hand is flexible. When study participants control a cursor by manipulating a tool held freely between the hands, the left hand becomes prime actor if the cursor moves directionally with the left-hand forces, whereas the right hand primarily acts if it moves with the opposing right-hand forces. In neurophysiological (electromyography, transcranial magnetic brain stimulation) and functional magnetic resonance brain imaging experiments we demonstrate that changes in hand assignment parallels a midline shift of lateralized activity in distal hand muscles, corticospinal pathways, and primary sensorimotor and cerebellar cortical areas. We conclude that the two hands can readily exchange roles as dominant actor in bimanual tasks. Spatial relationships between hand forces and goal motions determine hand assignments rather than habitual handedness. Finally, flexible role assignment of the hands is manifest at multiple levels of the motor system, from cortical regions all the way down to particular muscles.

  • 496.
    Johansson, Staffan
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Yelhekar, Tushar D.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Druzin, Michael
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Commentary: Chloride Regulation: a Dynamic Equilibrium Crucial for Synaptic Inhibition2016In: Frontiers in Cellular Neuroscience, ISSN 1662-5102, E-ISSN 1662-5102, Vol. 10, article id 182Article in journal (Refereed)
  • 497.
    Jonasson, Lars
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Umeå University, Faculty of Social Sciences, Centre for Demographic and Ageing Research (CEDAR).
    Nyberg, Lars
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology. Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Kramer, Arthur F
    Departments of Psychology and Mechanical and Industrial Engineering, Northeastern University, Boston, MA, USA.
    Axelsson, Jan
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Riklund, Katrine
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Boraxbekk, Carl-Johan
    Umeå University, Faculty of Social Sciences, Centre for Demographic and Ageing Research (CEDAR). Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Danish Research Centre for Magnetic Resonance, Copenhagen University Hospital, Hvidovre, Denmark..
    Aerobic fitness influences working memory updating via the striatal dopaminergic system in older adultsManuscript (preprint) (Other academic)
    Abstract [en]

    There is much evidence that dopamine is vital for cognitive functioning in aging. Here we tested the hypothesis that aerobic exercise and fitness influences dopaminergic neurotransmission in the striatum as measured by positron emission tomography (PET) and the non-displacable binding potential (BPND ) of [11C]raclopride, and in turn performance on offline working-memory updating tasks. In a sample of 58 older sedentary adults undergoing a six-months exercise intervention, aerobic exercise compared to stretching, toning, and resistance training did not have a differential effect on BPND . At baseline, higher aerobic fitness levels (VO2peak ) were associated with higher BPND  in the striatum. Following the intervention, for both forms of training, we found reduced BPND , indicating increased dopamine (DA), in a cluster in the anterior striatum in individuals with larger improvements in VO2peak . This reduction in BPND  mediated a positive indirect effect of VO2peak  on working-memory updating performance. Collectively these findings implicate DA as a neurocognitive mechanism explaining the positive effects of staying physically active at an old age for working memory.

  • 498.
    Jonasson, Lars
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Umeå University, Faculty of Social Sciences, Centre for Demographic and Ageing Research (CEDAR).
    Nyberg, Lars
    Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology. Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Kramer, Arthur
    Departments of Psychology and Mechanical and Industrial Engineering, Northeastern University, Boston, MA, USA.
    Lundquist, Anders
    Umeå University, Faculty of Social Sciences, Umeå School of Business and Economics (USBE), Statistics. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Riklund, Katrine
    Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Boraxbekk, Carl-Johan
    Umeå University, Faculty of Social Sciences, Centre for Demographic and Ageing Research (CEDAR). Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Danish Research Centre for Magnetic Resonance, Copenhagen University Hospital, Hvidovre, Denmark.
    Aerobic Exercise Intervention, CognitivePerformance, and Brain Structure: results from the Physical Influences on Brain in Aging (PHIBRA) Study2017In: Frontiers in Aging Neuroscience, ISSN 1663-4365, E-ISSN 1663-4365, Vol. 8, p. 1-15, article id 336Article in journal (Refereed)
    Abstract [en]

    Studies have shown that aerobic exercise has the potential to improve cognition and reduce brain atrophy in older adults. However, the literature is equivocal with regards to the specificity or generality of these effects. To this end, we report results on cognitive function and brain structure from a 6-month training intervention with 60 sedentary adults (64–78 years) randomized to either aerobic training or stretching and toning control training. Cognitive functions were assessed with a neuropsychological test battery in which cognitive constructs were measured using several different tests. Freesurfer was used to estimate cortical thickness in frontal regions and hippocampus volume. Results showed that aerobic exercisers, compared to controls, exhibited a broad, rather than specific, improvement in cognition as indexed by a higher “Cognitive score,” a composite including episodic memory, processing speed, updating, and executive function tasks (p = 0.01). There were no group differences in cortical thickness, but additional analyses revealed that aerobic fitness at baseline was specifically related to larger thickness in dorsolateral prefrontal cortex (dlPFC), and hippocampus volume was positively associated with increased aerobic fitness over time. Moreover, “Cognitive score” was related to dlPFC thickness at baseline, but changes in “Cognitive score” and dlPFC thickness were associated over time in the aerobic group only. However, aerobic fitness did not predict dlPFC change, despite the improvement in “Cognitive score” in aerobic exercisers. Our interpretation of these observations is that potential exercise-induced changes in thickness are slow, and may be undetectable within 6-months, in contrast to change in hippocampus volume which in fact was predicted by the change in aerobic fitness. To conclude, our results add to a growing literature suggesting that aerobic exercise has a broad influence on cognitive functioning, which may aid in explaining why studies focusing on a narrower range of functions have sometimes reported mixed results.

  • 499.
    Jonasson, Lars S.
    et al.
    Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Umeå University, Faculty of Medicine, Department of Radiation Sciences. Umeå University, Faculty of Social Sciences, Centre for Population Studies (CPS).
    Axelsson, Jan
    Umeå University, Faculty of Medicine, Department of Radiation Sciences. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Riklund, Katrine
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Braver, Todd S.
    Department of Psychology,Washington University, St Louis, MO 63130, USA.
    Ögren, Mattias
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Bäckman, Lars
    Aging Research Center, Karolinska Institute, SE-113 30 Stockholm, Sweden.
    Nyberg, Lars
    Umeå University, Faculty of Medicine, Department of Radiation Sciences. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Dopamine release in nucleus accumbens during rewarded task switching measured by [11C]raclopride2014In: NeuroImage, ISSN 1053-8119, E-ISSN 1095-9572, Vol. 99, p. 357-364Article in journal (Refereed)
    Abstract [en]

    Reward and motivation have positive influences on cognitive-control processes in numerous settings. Models of reward implicate corticostriatal loops and the dopamine (DA) system, with special emphasis on D2 receptors in nucleus accumbens (NAcc). In this study, 11 right-handed males (35-40 years) were scanned with positron emission tomography (PET) in a single [(11)C]raclopride dynamic scan during rewarded and non-rewarded task switching. Rewarded task switching (relative to baseline task switching) decreased [(11)C]raclopride binding in NAcc. Decreasing NAcc [(11)C]raclopride binding was strongly associated with task reaction time measures that reflect individual differences in effort and control strategies. Voxelwise analyses additionally revealed reward-related DA release in anterodorsal caudate, a region previously associated with task-switching. These PET findings provide evidence for striatal DA release during motivated cognitive control, and further suggest that NAcc DA release predicts the task reaction time benefits of reward incentives.

  • 500.
    Jonasson, Lars S.
    et al.
    Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Nyberg, Lars
    Umeå University, Faculty of Medicine, Department of Radiation Sciences. Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Axelsson, Jan
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Kramer, Arthur F.
    Riklund, Katrine
    Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Boraxbekk, Carl-Johan
    Umeå University, Faculty of Social Sciences, Centre for Demographic and Ageing Research (CEDAR). Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Danish Research Centre for Magnetic Resonance, Copenhagen University Hospital, Hvidovre, Denmark.
    Higher striatal D2-receptor availability in aerobically fit older adults but non-selective intervention effects after aerobic versus resistance training2019In: NeuroImage, ISSN 1053-8119, E-ISSN 1095-9572, Vol. 202, article id 116044Article in journal (Refereed)
    Abstract [en]

    There is much evidence that dopamine is vital for cognitive functioning in aging. Here we tested the hypothesis that aerobic exercise and fitness influence dopaminergic neurotransmission in the striatum, and in turn performance on offline working-memory updating tasks. Dopaminergic neurotransmission was measured by positron emission tomography (PET) and the non-displacable binding potential (BPND) of [11C]raclopride, i.e. dopamine (DA) D2-receptor (D2R) availability. Fifty-four sedentary older adults underwent a six-months exercise intervention, performing either aerobic exercise or stretching, toning, and resistance active control training. At baseline, higher aerobic fitness levels (VO2peak) were associated with higher BPND in the striatum, providing evidence of a link between an objective measure of aerobic fitness and D2R in older adults. BPND decreased substantially over the intervention in both groups but the intervention effects were non-selective with respect to exercise group. The decrease was several times larger than any previously estimated annual decline in D2R, potentially due to increased endogenous DA. Working-memory was unrelated to D2R both at baseline and following the intervention. To conclude, we provide partial evidence for a link between physical exercise and DA. Utilizing a PET protocol able to disentangle both D2R and DA levels could shed further light on whether, and how, aerobic exercise impacts the dopaminergic system in older adults.

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