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  • 201.
    Pruszynski, J. Andrew
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB). Department of Physiology and Pharmacology; Department of Psychology; Robarts Research Institute; Brain and Mind Institute, Western University, London, Canada.
    Flanagan, J. Randall
    Johansson, Roland S.
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB).
    Fast and accurate edge orientation processing during object manipulation2018Inngår i: eLIFE, E-ISSN 2050-084X, Vol. 7, artikkel-id e31200Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Quickly and accurately extracting information about a touched object’s orientation is a critical aspect of dexterous object manipulation. However, the speed and acuity of tactile edge orientation processing with respect to the fingertips as reported in previous perceptual studies appear inadequate in these respects. Here we directly establish the tactile system’s capacity to process edge-orientation information during dexterous manipulation. Participants extracted tactile information about edge orientation very quickly, using it within 200 ms of first touching the object. Participants were also strikingly accurate. With edges spanning the entire fingertip, edge-orientation resolution was better than 3° in our object manipulation task, which is several times better than reported in previous perceptual studies. Performance remained impressive even with edges as short as 2 mm, consistent with our ability to precisely manipulate very small objects. Taken together, our results radically redefine the spatial processing capacity of the tactile system.

  • 202.
    Pruszynski, J Andrew
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Fysiologi.
    Johansson, Roland S
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Fysiologi.
    Edge-orientation processing in first-order tactile neurons2014Inngår i: Nature Neuroscience, ISSN 1097-6256, E-ISSN 1546-1726, Vol. 17, nr 10, s. 1404-1409Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    A fundamental feature of first-order neurons in the tactile system is that their distal axon branches in the skin and forms many transduction sites, yielding complex receptive fields with many highly sensitive zones. We found that this arrangement constitutes a peripheral neural mechanism that allows individual neurons to signal geometric features of touched objects. Specifically, we observed that two types of first-order tactile neurons that densely innervate the glabrous skin of the human fingertips signaled edge orientation via both the intensity and the temporal structure of their responses. Moreover, we found that the spatial layout of a neuron's highly sensitive zones predicted its sensitivity to particular edge orientations. We submit that peripheral neurons in the touch-processing pathway, as with peripheral neurons in the visual-processing pathway, perform feature extraction computations that are typically attributed to neurons in the cerebral cortex.

  • 203.
    Pruszynski, J Andrew
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Fysiologi. Centre for Neuroscience Studies, Queen's University, Kingston, Ontario K7L 3N6, Canada.
    Omrani, Mohsen
    Centre for Neuroscience Studies, Queen's University, Kingston, Ontario K7L 3N6, Canada.
    Scott, Stephen H
    Centre for Neuroscience Studies, Departments of Biomedical and Molecular Sciences, and Medicine, Queen's University, Kingston, Ontario K7L 3N6, Canada.
    Goal-dependent modulation of fast feedback responses in primary motor cortex2014Inngår i: Journal of Neuroscience, ISSN 0270-6474, E-ISSN 1529-2401, Vol. 34, nr 13, s. 4608-4617Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Many human studies have demonstrated that rapid motor responses (i.e., muscle-stretch reflexes) to mechanical perturbations can be modified by a participant's intended response. Here, we used a novel experimental paradigm to investigate the neural mechanisms that underlie such goal-dependent modulation. Two monkeys positioned their hand in a central area against a constant load and responded to mechanical perturbations by quickly placing their hand into visually defined spatial targets. The perturbation was chosen to excite a particular proximal arm muscle or isolated neuron in primary motor cortex and two targets were placed so that the hand was pushed away from one target (OUT target) and toward the other (IN target). We chose these targets because they produced behavioral responses analogous to the classical verbal instructions used in human studies. A third centrally located target was used to examine responses with a constant goal. Arm muscles and neurons robustly responded to the perturbation and showed clear goal-dependent responses ∼35 and 70 ms after perturbation onset, respectively. Most M1 neurons and all muscles displayed larger perturbation-related responses for the OUT target than the IN target. However, a substantial number of M1 neurons showed more complex patterns of target-dependent modulation not seen in muscles, including greater activity for the IN target than the OUT target, and changes in target preference over time. Together, our results reveal complex goal-dependent modulation of fast feedback responses in M1 that are present early enough to account for goal-dependent stretch responses in arm muscles.

  • 204.
    Radovanovic, Dina
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi.
    Peikert, Kevin
    Lindström, Mona
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi.
    Pedrosa Domellöf, Fatima
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi. Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Oftalmiatrik.
    Sympathetic innervation of human muscle spindles2015Inngår i: Journal of Anatomy, ISSN 0021-8782, E-ISSN 1469-7580, Vol. 226, nr 6, s. 542-548Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The aim of the present study was to investigate the presence of sympathetic innervation in human muscle spindles, using antibodies against neuropeptide Y (NPY), NPY receptors and tyrosine hydroxylase (TH). A total of 232 muscle spindles were immunohistochemically examined. NPY and NPY receptors were found on the intrafusal fibers, on the blood vessels supplying muscle spindles and on free nerve endings in the periaxial space. TH-immunoreactivity was present mainly in the spindle nerve and vessel. This is, to our knowledge, the first morphological study concerning the sympathetic innervation of the human muscle spindles. The results provide anatomical evidence for direct sympathetic innervation of the intrafusal fibers and show that sympathetic innervation is not restricted to the blood vessels supplying spindles. Knowledge about direct sympathetic innervation of the muscle spindle might expand our understanding of motor and proprioceptive dysfunction under stress conditions, for example, chronic muscle pain syndromes.

  • 205. Recirovic-Agic, Mediha
    et al.
    Jönsson, Sofia
    Tveitarås, Maria K.
    Skogstrand, Trude
    Karlsen, Tine, V
    Lidén, Åsa
    Leh, Sabine
    Ericsson, Madelene
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap.
    Nilsson, Stefan K.
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap.
    Reed, Rolf K.
    Hultstrom, Michael
    Time course of decompensation after angiotensin II and high-salt diet in Balb/CJ mice suggests pulmonary hypertension-induced cardiorenal syndrome2019Inngår i: American Journal of Physiology. Regulatory Integrative and Comparative Physiology, ISSN 0363-6119, E-ISSN 1522-1490, Vol. 316, nr 5, s. R563-R570Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The genetic background of a mouse strain determines its susceptibility to disease. C57BL/6J and Balb/CJ are two widely used inbred mouse strains that we found react dramatically differently to angiotensin II and high-salt diet (ANG II + Salt). Balb/CJ show increased mortality associated with anuria and edema formation while C57BL/6J develop arterial hypertension but do not decompensate and die. Clinical symptoms of heart failure in Balb/CJ mice gave the hypothesis that ANG II + Salt impairs cardiac function and induces cardiac remodeling in male Balb/CJ but not in male C57BL/6J mice. To test this hypothesis, we measured cardiac function using echocardiography before treatment and every day for 7 days during treatment with ANG II + Salt. Interestingly, pulsed wave Doppler of pulmonary artery flow indicated increased pulmonary vascular resistance and right ventricle systolic pressure in Balb/CJ mice, already 24 h after ANG II + Salt treatment was started. In addition, Balb/CJ mice showed abnormal diastolic filling indicated by reduced early and late filling and increased isovolumic relaxation time. Furthermore, Balb/CJ exhibited lower cardiac output compared with C57BL/6J even though they retained more sodium and water, as assessed using metabolic cages. Left posterior wall thickness increased during ANG II + Salt treatment but did not differ between the strains. In conclusion, ANG II + Salt treatment causes early restriction of pulmonary flow and reduced left ventricular filling and cardiac output in Balb/CJ, which results in fluid retention and peripheral edema. This makes Balb/CJ a potential model to study the adaptive capacity of the heart for identifying new disease mechanisms and drug targets.

  • 206.
    Salami, Alireza
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Fysiologi. Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI).
    Eriksson, Johan
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Fysiologi. Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI).
    Kompus, Kristiina
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi. Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Fysiologi.
    Habib, Reza
    Southern Illinois University , Carbondale.
    Kauppi, Karolina
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Fysiologi. Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI).
    Nyberg, Lars
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi. Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Fysiologi.
    Characterizing the neural correlates of modality-specific and modality-independent accessibility and availability signals in memory using partial-least squares2010Inngår i: NeuroImage, ISSN 1053-8119, E-ISSN 1095-9572, Vol. 52, nr 2, s. 686-698Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Previous studies have shown that information that currently cannot be retrieved but will be retrieved on a subsequent, more supported task (i.e. is available but not accessible) has a distinct neural signature compared with non-available information. For verbal paired-associates, an availability signal has been revealed in left middle temporal cortex, an area potentially involved in the storage of such information, raising the possibility that availability signals are expressed in modality-specific storage sites. In the present study subjects encoded pictures and sounds representing concrete objects. One day later, during fMRI scanning, a verbal cued-recall task was administrated followed by a post-scan recognition task. Items remembered on both tasks were classified as accessible; items not remembered on the first but on the second task were classified as available; and items not remembered on any of the tasks were classified as not available. Multivariate partial-least-squares analyses revealed a modality-independent accessibility network with dominant contributions of left inferior parietal cortex, left inferior frontal cortex, and left hippocampus. Additionally, a modality-specific availability network was identified which included increased activity in visual regions for available pictorial information and in auditory regions for available sound information. These findings show that availability in memory, at least in part, is characterized by systematic changes in brain activity in sensory regions whereas memory access reflects differential activity in a modality-independent, conceptual network, thus indicating qualitative differences between availability and accessibility in memory.

  • 207.
    Salami, Alireza
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Fysiologi. Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI).
    Eriksson, Johan
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Fysiologi. Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI).
    Nilsson, Lars-Göran
    Stockholm University.
    Nyberg, Lars
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi. Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Fysiologi. Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI).
    Age-related white matter microstructural differences partly mediate age-related decline in processing speed but not cognition2012Inngår i: Biochimica et Biophysica Acta, ISSN 0006-3002, E-ISSN 1878-2434, Vol. 1822, nr 3, s. 408-415Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Aging is associated with declining cognitive performance as well as structural changes in brain gray and white matter (WM). The WM deterioration contributes to a disconnection among distributed brain networks and may thus mediate age-related cognitive decline. The present diffusion tensor imaging (DTI) study investigated age-related differences in WM microstructure and their relation to cognition (episodic memory, visuospatial processing, fluency, and speed) in a large group of healthy subjects (n=287) covering 6 decades of the human life span. Age related decreases in fractional anisotropy (FA) and increases in mean diffusivity (MD) were observed across the entire WM skeleton as well as in specific WM tracts, supporting the WM degeneration hypothesis. The anterior section of the corpus callosum was more susceptible to aging compared to the posterior section, lending support to the anterior-posterior gradient of WM integrity in the corpus callosum. Finally, and of critical interest, WM integrity differences were found to mediate age-related reductions in processing speed but no significant mediation was found for episodic memory, visuospatial ability, or fluency. These findings suggest that compromised WM integrity is not a major contributing factor to declining cognitive performance in normal aging. This article is part of a Special Issue entitled: Imaging Brain Aging and Neurodegenerative disease.

  • 208.
    Salami, Alireza
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Fysiologi. Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI).
    Eriksson, Johan
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Fysiologi. Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI).
    Nyberg, Lars
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Fysiologi. Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI).
    Opposing effects of aging on large-scale brain systems for memory encoding and cognitive control2012Inngår i: Journal of Neuroscience, ISSN 0270-6474, E-ISSN 1529-2401, Vol. 32, nr 31, s. 10749-10757Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Episodic memory declines with advancing age. Neuroimaging studies have associated such decline to age-related changes in general cognitive-control networks as well as to changes in process-specific encoding or retrieval networks. To assess the specific influence of aging on encoding and retrieval processes and associated brain systems, it is vital to dissociate encoding and retrieval from each other and from shared cognitive-control processes. We used multivariate partial-least-squares to analyze functional magnetic resonance imaging data from a large population-based sample (n = 292, 25-80 years). The participants performed a face-name paired-associates task and an active baseline task. The analysis revealed two significant network patterns. The first reflected a process-general encoding-retrieval network that included frontoparietal cortices and posterior hippocampus. The second pattern dissociated encoding and retrieval networks. The anterior hippocampus was differentially engaged during encoding. Brain scores, representing whole-brain integrated measures of how strongly an individual recruited a brain network, were correlated with cognitive performance and chronological age. The scores from the general cognitive-control network correlated negatively with episodic memory performance and positively with age. The encoding brain scores, which strongly reflected hippocampal functioning, correlated positively with episodic memory performance and negatively with age. Univariate analyses confirmed that bilateral hippocampus showed the most pronounced activity reduction in older age, and brain structure analyses found that the activity reduction partly related to hippocampus atrophy. Collectively, these findings suggest that age-related structural brain changes underlie age-related reductions in the efficient recruitment of a process-specific encoding network, which cascades into upregulated recruitment of a general cognitive-control network.

  • 209. Sasaki, Shigeto
    et al.
    Naito, Kimisato
    Yoshimura, Kazuya
    Isa, Tadashi
    Seki, Kazuhiko
    Pettersson, Lars-Gunnar
    Alstermark, Bror
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Fysiologi.
    Ohki, Yukari
    Cortico-motoneuronal system and dexterous finger movements: reply2004Inngår i: Journal of Neurophysiology, ISSN 0022-3077, E-ISSN 1522-1598, Vol. 92, nr 6, s. 3601-3603Artikkel i tidsskrift (Fagfellevurdert)
  • 210.
    Schlader, Zachary J.
    et al.
    Texas Hlth Presbyterian Hosp Dallas, Inst Exercise & Environm Med, Dallas, TX 75231 USA.
    Lucas, Rebekah A. I.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Epidemiologi och global hälsa. Texas Hlth Presbyterian Hosp Dallas, Inst Exercise & Environm Med, Dallas, TX 75231 USA.
    Pearson, James
    Texas Hlth Presbyterian Hosp Dallas, Inst Exercise & Environm Med, Dallas, TX 75231 USA.
    Crandall, Craig G.
    Texas Hlth Presbyterian Hosp Dallas, Inst Exercise & Environm Med, Dallas, TX 75231 USA.
    Hyperthermia does not alter the increase in cerebral perfusion during cognitive activation2013Inngår i: Experimental Physiology, ISSN 0958-0670, E-ISSN 1469-445X, Vol. 98, nr 11, s. 1597-1607Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    This study tested the hypothesis that hyperthermia attenuates the increase in cerebral perfusion during cognitive activation. Mean middle cerebral artery blood velocity (MCAV(mean)) served as an index of cerebral perfusion, while the nBack test (a test of working memory) was the cognitive task. Hyperthermia was characterized by elevations (P < 0.001) in skin (by 5.0 +/- 0.8 degrees C) and intestinal temperatures (by 1.3 +/- 0.1 degrees C) and reductions (P < 0.020) in mean arterial pressure (by 11 +/- 10 mmHg), end-tidal CO2 tension (by 3 +/- 6 mmHg) and MCAVmean (by 10 +/- 9 cm s(-1)). Hyperthermia had no influence on nBack test performance (mean difference from normothermia to hyperthermia, -1 +/- 11%; P = 0.276) or, counter to the hypothesis, the increase in MCAV(mean) during nBack testing (mean difference from normothermia to hyperthermia: 0 +/- 16 cm s(-1); P = 0.608). These findings indicate that the capacity to increase cerebral perfusion during cognitive activation is unaffected by hyperthermia.

  • 211.
    Schrottmaier, Waltraud C.
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi. Institute for Vascular Biology and Thrombosis Research, Medical University of Vienna, Austria.
    Salzmann, M.
    Badrnya, S.
    Morava, S.
    Luik, A-L
    Kral-Pointner, J. B.
    Mussbacher, M.
    Karlsson, M.
    Forsell, Mattias
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi.
    Assinger, A.
    Platelet-stored antibodies potently diminish viral infection in vitro and in vivo2019Inngår i: Acta Physiologica, ISSN 1748-1708, E-ISSN 1748-1716, Vol. 227, nr S718, s. 187-187Artikkel i tidsskrift (Annet vitenskapelig)
    Abstract [en]

    Besides their primary role in haemostasis, platelets are actively involved in immune responses as they respond to various inflammatory stimuli, including microbial infection. Further, platelets contain intracellular IgG, but their physiologic function remains unknown. Thus, we aimed to elucidate the function of platelet-derived IgGs and their effect on viral infections. Human and murine platelets contained IgG which were released upon shear stress. However, IgG loss did not correlate with P-Selectin exposure or CXCL4 release and α-granule deficient (Nbeal2-/-) platelets failed to show reduced IgG content and release, indicating an extragranular IgG storage site within platelets. While platelet IgG could derive from megakaryocytes that have taken up IgG from the bone marrow microenvironment, naïve platelets also took up IgG directly from plasma in vitro and in vivo. Murine platelets from anti-IAV IgG seropositive mice reduced IAV infection in vitro and in vivo more efficiently than plasma containing comparable IgG levels. Further, human platelets from anti-CMV IgG seropositive but not seronegative donors also potently neutralized in vitro CMV-infection of HUVEC under microvascular shear stress. Our data indicate that IgG storage in platelets may not be restricted to α-granules. Further, our results show that platelets have the potential to mediate potent IgG-mediated antiviral effects both in vitro and in vivo directly at foci of infection. This indicates that platelet-derived IgG may represent a yet unexplored mechanism for focused serological immunity.

  • 212.
    Scott, G
    et al.
    McGill University, Montréal and Université de Montréal.
    Westberg, Karl-Gunnar
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Fysiologi.
    Vrentzos, N
    McGill University, Montréal.
    Kolta, A
    Université de Montréal.
    Lund, J P
    McGill University, Montréal and Université de Montréal.
    Effect of lidocaine and NMDA injections into the medial pontobulbar reticular formation on mastication evoked by cortical stimulation in anaesthetized rabbits2003Inngår i: European Journal of Neuroscience, ISSN 0953-816X, E-ISSN 1460-9568, Vol. 17, nr 10, s. 2156-2162Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Neurons of the dorsal nucleus reticularis pontis caudalis (nPontc) fire rhythmically during fictive mastication, while neurons of the ventral half tend to fire tonically (Westberg et al., 2001). This paper describes the changes in the pattern of rhythmical mastication elicited by stimulation of the sensorimotor cortex during inhibition or excitation of neurons in this nucleus and adjacent parts of nucleus reticularis gigantocellularis (Rgc) in the anaesthetized rabbit. Masticatory movements and electromyographic (EMG) activity of the masseter and digastric muscles produced by cortical stimulation were recorded before, during and after injections of a local anaesthetic (lidocaine) or excitatory amino acid N-methyl-d-aspartate (NMDA) into nPontc and Rgc through a microsyringe with attached microelectrode to record neuronal activity. Lidocaine inhibited local neurons and modified the motor program, and the effects varied with the site of injection. Most injections into the ventral half of nPontc increased cycle duration, digastric burst duration and burst area. The action of lidocaine in dorsal nPontc was more variable, although burst duration and area were often decreased. The effects on the muscle activity were always bilateral. Lidocaine block of the rostromedial part of Rgc had no effect on movements or on EMGs. Injections of NMDA excited local neurons and when injected into ventral nPontc, it completely blocked mastication. Dorsal injections either had no effect or increased cycle frequency, while decreasing burst duration and area. No increases in EMG burst duration or area were observed with NMDA. Our findings suggest that neurons of ventral nPontc tonically inhibit other parts of the central pattern generator during mastication, while dorsal neurons have mixed effects. We incorporated these findings into a new model of the masticatory central pattern generator.

  • 213. Seligsohn, E. E.
    et al.
    Koskinen, Lars-Owe D.
    Department of Physiology and Medical Biophysics, Biomedical Centre, Uppsala University, Uppsala, Sweden.
    Effects of alpha 2-adrenoceptor blockade and thyrotropin-releasing hormone (TRH) on the cardiovascular system in the rabbit.1991Inngår i: Acta Physiologica Scandinavica, ISSN 0001-6772, E-ISSN 1365-201X, Vol. 143, nr 2, s. 187-194Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The effects of two different doses of thyrotropin-releasing hormone on regional blood flows were studied in urethane-anaesthetized rabbits pretreated with the alpha 2-adrenergic antagonists yohimbine and idazoxan. The effects of yohimbine were also studied using unanaesthetized rabbits. Blood flow measurements were performed using the tracer microsphere method. Thyrotropin-releasing hormone was injected i.v. at a dose of either 0.1 mg kg-1 or 2.0 mg kg-1. Yohimbine and idazoxan did not modify the effect of thyrotropin-releasing hormone on mean arterial blood pressure. In the anaesthetized animals, blockade of the alpha 2-adrenoceptors resulted in a vasoconstriction in several peripheral organs and the vasoconstriction increased after thyrotropin-releasing hormone administration. Pretreament with yohimbine reduced total cerebral blood flow moderately and in such animals thyrotropin-releasing hormone elicited only minor cerebral blood flow effects. Pretreatment with idazoxan did not reduce the total cerebral blood flow and in such animals it increased from 53 +/- 1 to 75 +/- 4 g min-1 100 g-1 (P less than 0.01) after the administration of the lower dose of thyrotropin-releasing hormone and from 64 +/- 5 to 112 +/- 17 g min-1 100 g-1 (P less than 0.01) after the higher dose. In the conscious animals, yohimbine caused an increase in mean arterial blood pressure and heart rate. Vascular resistance increased in several organs. The cerebral blood flow decreased in white matter (P less than 0.05) and the caudate nucleus (P less than 0.05). The results indicate that there is a yohimbine-sensitive mechanism involved in the cerebrovasodilating effect of thyrotropin-releasing hormone in anaesthetized rabbits.(ABSTRACT TRUNCATED AT 250 WORDS)

  • 214.
    Shah, Farhan
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB).
    Berggren, Diana
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Öron- näs- och halssjukdomar.
    Holmlund, Thorbjörn
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Öron- näs- och halssjukdomar.
    Levring Jäghagen, Eva
    Umeå universitet, Medicinska fakulteten, Institutionen för odontologi.
    Stål, Per
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB).
    Unique expression of cytoskeletal proteins in human soft palate muscles2016Inngår i: Journal of Anatomy, ISSN 0021-8782, E-ISSN 1469-7580, Vol. 228, nr 3, s. 487-494Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The human oropharyngeal muscles have a unique anatomy with diverse and intricate functions. To investigate if this specialization is also reflected in the cytoarchitecture of muscle fibers, intermediate filament proteins and the dystrophin-associated protein complex have been analyzed in two human palate muscles, musculus uvula (UV) and musculus palatopharyngeus (PP), with immunohistochenmical and morphological techniques. Human limb muscles were used as reference. The findings show that the soft palate muscle fibers have a cytoskeletal architecture that differs from the limb muscles. While all limb muscles showed immunoreaction for a panel of antibodies directed against different domains of cytoskeletal proteins desmin and dystrophin, a subpopulation of palate muscle fibers lacked or had a faint immunoreaction for desmin (UV 11.7% and PP 9.8%) and the C-terminal of the dystrophin molecule (UV 4.2% and PP 6.4%). The vast majority of these fibers expressed slow contractile protein myosin heavy chain I. Furthermore, an unusual staining pattern was also observed in these fibers for β-dystroglycan, caveolin-3 and neuronal nitric oxide synthase nNOS, which are all membrane-linking proteins associated with the dystrophin C-terminus. While the immunoreaction for nNOS was generally weak or absent, β-dystroglycan and caveolin-3 showed a stronger immunostaining. The absence or a low expression of cytoskeletal proteins otherwise considered ubiquitous and important for integration and contraction of muscle cells indicate a unique cytoarchitecture designed to meet the intricate demands of the upper airway muscles. It can be concluded that a subgroup of muscle fibers in the human soft palate appears to have special biomechanical properties, and their unique cytoarchitecture must be taken into account while assessing function and pathology in oropharyngeal muscles.

  • 215.
    Silfvenius, Herbert
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Fysiologi.
    Projections to the cat cerebral cortex from fore- and hind limb group I muscle afferents1972Doktoravhandling, med artikler (Annet vitenskapelig)
  • 216.
    Sjölander, Per
    Umeå universitet.
    A sensory role for the cruciate ligaments: regulation of joint stability via reflexes onto the γ-muscle-spindle system1989Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    Reflex effects evoked by graded electrical stimulation of the posterior articular nerves (PAN) of the ipsi- and contralateral knee joints were investigated using both micro-electrode recordings from 7 - motoneurones and recordings from single muscle muscle spindle afferents. Spindle afferent responses were also recorded using natural stimulation of different types of receptors, to elucidate if the articular reflexes onto the y -motoneurones were potent enough to significantly alter the muscle spindle afferent activity. Stretches of the ipsilateral posterior (PCL) and anterior (ACL) cruciate ligaments, pressure on the ipsi- and contralateral knee and ankle joint capsules, and passive flexion/extension movements of the joints in the contralateral hind limb were performed. The occurrance of different sensory endings in the ACL and PCL was examined using gold chloride staining for neuronal elements. All experiments were performed on chloralose anaesthetized cats.

    More than 90% of the static and dynamic y -motoneurones were responsive to electrical stimulation of the PAN. Most 7-cells responded to low intensity electrical stimulation. Excitatoiy reflex effects predominated on both static and dynamic posterior biceps-semitendinosus (PBSt) 7 -cells, while excitatory and inhibitory effects occurred with an about equal frequency on triceps-plantaris (GS) 7-cells. The fastest segmental route for excitatory PAN effects on hind limb 7-motoneurones seems to be di- or trisynaptic, while the path for inhibitory effects seems to be at least one synaps longer.

    Physiological stimulations of ipsi- and contralateral joint capsules and of ipsilateral cruciate ligaments were all found to evoke frequent and potent changes in spindle afferent responses from the GS and PBSt muscles. It was shown that these effects were due to reflexes onto dynamic and static fusimotor neurones caused by physiological activation of articular sensory endings. Both ipsi- and contralateral joint receptor stimulation evoked excitatory as well as inhibitory fusimotor effects. The highest responsiveness was found during stimula­tion of the cruciate ligaments, i.e. 58% for GS and 47% for PBSt primary spindle afferents to PCL stimula­tion, and 73% for GS and 55% for PBSt primary spindle afferents to ACL stimulation. Significant altera­tions in spindle afferent activity was encountered at very low traction forces applied to the cruciate ligaments (5-10 N). The low thresholds, the tonic character of the stimuli, and the fact that different types of sensory endings were demonstrated in the cruciate ligaments (i.e. Ruffini endings, Pacinian corpuscles, Golgi ten­don organ like endings and free nerve endings), indicate that the fusimotor effects observed were caused by activation of slowly adapting mechanoreceptors, most likely Ruffini endings and/or Golgi tendon organ like endings.

    The potent reflex effects on the muscle spindle afferents elicited by increased tension in the cruciate ligaments indicate that these ligaments may play a more important sensory role that hitherto believed, and it is suggested that they may be important in the regulation of the stiffness of muscles around the knee joint, and thereby for the joint stability. The possible clinical relevance and the mechanisms by which joint receptor afferents, via adjustment of the muscle stiffness, may control joint stability are discussed.

  • 217.
    Song, Yafeng
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB).
    Cross transfer effects after unilateral muscle overuse: an experimental animal study about alterations in the morphology and the tachykinin system of muscles2013Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    Unilateral exercise can produce certain contralateral strength effects. Deleterious events can be cross-transferred as well, as illustrated by a strict symmetry in some chronic inflammatory diseases. To date, knowledge on the effects of marked overuse of skeletal muscles is limited, and there is largely no information if unilateral overuse affects the contralateral muscles. In view of this, the present study was undertaken to test the hypothesis that unilateral muscle overuse causes alterations in tissue structure and the tachykinin system, with a focus on substance P (SP), not only in the exercised muscles, but also in the contralateral muscles. SP is a well-known neuromodulator that is known to be proinflammatory.

    An experimental rabbit model with unilateral muscle overuse of the soleus and gastrocnemius muscles caused by exercise via electrical muscle stimulation (E/EMS) was used. In total, 40 rabbits were randomly divided into seven groups of which two groups served as controls. The rabbits were anaesthetized and then set on a “kicking machine” to perform exercise via EMS for 2h every second day. Experimental periods for groups 1-3 were 1, 3 and 6w, respectively, whereas groups 4-6 were exercised for 1w but also subjected to injections in the peritendinous tissue with SP, NaCL, Captopril (C), an ACE inhibitor, and DL-Thiorphan (Th) which inhibits the activity of neural endopeptidase. One group was not subjected to the experiment at all. The day after the last session of E/EMS, the soleus muscle and the gastrocnemius muscle from both legs were collected for analysis. Alterations in muscle structure and the tachykinin system were analyzed with enzyme and immunohistochemical techniques, in situ hybridization and EIA methods.

    After 1w of E/EMS, focal areas of the exercised muscles contained a mild infiltration of inflammatory cells (myositis) and small morphological changes. After 3 and 6w of E/EMS, distinct myositis and muscle changes were bilaterally present in focal areas of both muscles. The structural changes, which mainly were observed in myositis areas, consisted of increased fiber size variability, split fibers, internal myonuclei, necrotic fibers, fibrosis, fat infiltration, and small fibers containing developmental MyHCs. Bilateral morphological changes, such as loss of axons, were also observed in nerves. In addition, expressions of tachykinin and the SP-preferred receptor, the neurokinin-1 (NK-1R), were bilaterally upregulated in nerve structures and blood vessel walls.  Infiltrating white blood cells exhibited tachykinin–like and NK-1R immunoreactivity. NK-1R immunoreactions were also found in necrotic and regenerating muscle fibers.

    The concentration of tachykinin (SP) was significantly increased in both soleus and gastrocnemius muscles after E/EMS. There was a significant correlation between the two sides in concentration of tachykinin and in the intensity of tachykinin-like immunoreaction in blood vessel walls. The muscle fiber size and capillary supply of fibers were bilaterally decreased after 3w of EMS. The myositis areas contained an increased number of vessels with a larger size than capillaries, while areas with increased amount of connective tissue contained a very low number of capillaries. A bilateral fiber type shift against a lower proportion of slow MyHCI fibers and higher proportion of fast MyHCII fibers was observed in both muscles. The local injections of C+Th and SP+C+Th led to marked structural changes in the muscle tissue and marked increased NK-1R and tachykinin-like immunoreactivity in the myositis areas and increased tachykinin concentration in the tissue.

    In conclusion, the repetitive unilateral muscle overuse caused by E/EMS led overtime to muscle injury and myositis. The affected areas contained both degenerative and regenerative alterations in the muscle tissue and nerves, and an upregulation of the tachykinin system. Most interestingly, the changes not only occurred in the exercised side, but also in the homologous contralateral muscles. The tachykinin system appears to be an important factor in the processes of crossover effects. 

  • 218.
    Song, Yafeng
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi.
    Forsgren, Sture
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi.
    Liu, Jing Xia
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi.
    Yu, Jiguo
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Idrottsmedicin.
    Stål, Per
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi.
    Unilateral muscle overuse causes bilateral changes in muscle fibre composition and vascular supplyManuskript (preprint) (Annet vitenskapelig)
  • 219.
    Song, Yafeng
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi.
    Stål, Per
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi.
    Lorentzon, Ronny
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Idrottsmedicin.
    Backman, C
    Yu, Jiguo
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Idrottsmedicin.
    Forsgren, Sture
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi.
    Experimental studies favour that tachykinins are involved in the process of myositis and muscle derangement in an overuse animal modelManuskript (preprint) (Annet vitenskapelig)
  • 220.
    Spang, Christoph
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi.
    Alfredson, Håkan
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Idrottsmedicin.
    Ferguson, Mark
    Centre for Sports Medicine and Orthopaedics, Rosebank Johannesburg.
    Roos, Beverley
    Centre for Sports Medicine and Orthopaedics, Rosebank Johannesburg.
    Bagge, Johan
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi.
    Forsgren, Sture
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi.
    The plantaris tendon in association with mid-portion Achilles tendinosis: tendinosis-like morphological features and presence of a non-neuronal cholinergic system2013Inngår i: Histology and Histopathology, ISSN 0213-3911, E-ISSN 1699-5848, Vol. 28, s. 623-632Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The plantaris tendon is often neglected in morphological/clinical studies on the lower extremity. There is, however, clinical evidence that the plantaris tendon is involved in cases with Achilles midportion tendinopathy/tendinosis. It is nevertheless unclear if the plantaris tendon exhibits tendinosis-like features in this situation. We therefore investigated the plantaris tendon of patients with midportion Achilles tendinosis when the plantaris tendon was found to be located very close to or invaginated into the Achilles tendon, a situation which very often has been found to be the case. There was a very large number of tenocytes in the tendon tissue and the tenocytes showed abnormal and irregular appearances, exhibiting widened/rounded and wavy appearances, and were frequently lined up in rows. These features are characteristic features in Achilles tendinosis tendons. The tendon cells showed a distinct immunoreaction for the acetylcholine (ACh) -producing enzyme choline acetyltransferase (ChAT). Frequent fibroblasts were found in the loose connective tissue and these cells also showed a marked ChAT immunoreaction. The study shows that the plantaris tendon is morphologically affected in a similar way to the Achilles tendon in cases with midportion Achilles tendinosis and medial pain. The plantaris tendon may accordingly be a co-factor in these cases. The results also favour that there is a local ACh production both within the tendon tissue of the plantaris tendon and in the loose connective tissue. In conclusion, it is evident that plantaris tendons lying invaginated into or very close to the Achilles tendon in cases with midportion Achilles tendinosis show similar tendinosis features, as previously shown for the Achilles tendon itself in these cases.

  • 221.
    Spang, Christoph
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi.
    Backman, L
    LeRoux, S
    Forsgren, S
    Danielson, P
    Plantaris tendon tissue of tendinosis patients displays a glutamate signallingmachinery that may influence tenocyte phenotypeManuskript (preprint) (Annet vitenskapelig)
  • 222.
    Spang, Christoph
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi.
    Harandi, Vahid M
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi.
    Alfredsson, Håkan
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering. Pure Sports Medicine Clinic, London, UK; ISEH, UCLH, London, UK.
    Forsgren, Sture
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi.
    Marked innervation but also signs of nerve degeneration in between the Achilles and plantaris tendons and presence of innervation within the plantaris tendon in midportion Achilles tendinopathy2015Inngår i: Journal of Musculoskeletal and Neuronal Interactions - JMNI, ISSN 1108-7161, Vol. 15, nr 2, s. 197-206Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objectives: The plantaris tendon is increasingly recognised as an important factor in midportion Achilles tendinopathy. Its innervation pattern is completely unknown. Methods: Plantaris tendons (n=56) and associated peritendinous tissue from 46 patients with midportion Achilles tendinopathy and where the plantaris tendon was closely related to the Achilles tendon were evaluated. Morphological evaluations and stainings for nerve markers [general (PGP9.5), sensory (CGRP), sympathetic (TH)], glutamate NMDA receptor and Schwann cells (S-100β) were made. Results: A marked innervation, as evidenced by evaluation for PGP9.5 reactions, occurred in the peritendinous tissue located between the plantaris and Achilles tendons. It contained sensory and to some extent sympathetic and NMDAR1-positive axons. There was also an innervation in the zones of connective tissue within the plantaris tendons. Interestingly, some of the nerve fascicles showed a partial lack of axonal reactions. Conclusion: New information on the innervation patterns for the plantaris tendon in situations with midportion Achilles tendinopathy has here been obtained. The peritendinous tissue was found to be markedly innervated and there was also innervation within the plantaris tendon. Furthermore, axonal degeneration is likely to occur. Both features should be further taken into account when considering the relationship between the nervous system and tendinopathy

  • 223.
    Spang, Christoph
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi. Dr. Alfen Orthopaedic Spine Center, Würzburg, Germany.
    Renström, Lina
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi.
    Alfredson, Håkan
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Idrottsmedicin. Pure Sports Medicine Clinic, London, UK ; ISEH, UCLH, London, UK.
    Forsgren, Sture
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi.
    Marked expression of TNF receptors in human peritendinous tissues including in nerve fascicles with axonal damage: Studies on tendinopathy and tennis elbow2017Inngår i: Journal of Musculoskeletal and Neuronal Interactions - JMNI, ISSN 1108-7161, Vol. 17, nr 3, s. 226-236Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: The peritendinous connective tissues can have importance in chronic tendon pain. Recently cytokine TNF-alpha has been suggested to be involved in tendinopathic processes. It is not known how TNF-alpha and its receptors TNFR1 and TNFR2 are expressed in peritendinous tissues.

    Methods: The objective for this study was to immunohistochemically evaluate the expression patterns of these in the peritendinous tissue located between the plantaris and Achilles tendons and the one located superficially to the extensor origin at the elbow region for patients with tendinopathy/tennis elbow.

    Results: The nerve fascicles were of two types, one type being homogenously stained for the nerve markers beta III-tubulin and neurofilament and the other showing deficits for these suggesting features of axonal damage. Much more distinct TNFR1/TNFR2 immunoreactions were seen for the latter nerve fascicles. TNFR1 was seen in axons, TNFR2 mainly in Schwann cells. TNFR1 and particularly TNFR2 were seen in walls of parts of blood vessels. The dispersed cells showed frequently TNFR1 and TNFR2 immunoreactivity.

    Discussion: These findings suggest that TNF-alpha can be related to degenerative events but also attempts for healing concerning the nerve structures. The marked expression of the TNF-alpha system in the peritendinous tissue suggests an impact of TNF-alpha in tendinopathy/tennis elbow.

  • 224. Stein, L.
    et al.
    Bergdahl, M.
    Pettersen, K. S.
    Bergdahl, Jan
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Fysiologi.
    Exploring the association between oral health literacy and alexithymia2015Inngår i: Community Dental Health, ISSN 0265-539X, Vol. 32, nr 3, s. 143-147Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Low health literacy and alexithymia have separately been emphasized as barriers to patient-practitioner communication, but the association between the two concepts has not been explored. Objective: To test the hypothesis that low oral health literacy and alexithymia are associated. Method: Adults (n=127) aged 21-80 years (56% women) participated in this cross-sectional study. Oral health literacy was assessed using the interview-based Adult Health Literacy Instrument for Dentistry (AHLID) with scores from 1-5. The self-administered Toronto Alexithymia Scale (TAS-20) was used to assess three distinct TAS-20 factors and TAS-20 total score. Results: Significant negative correlations between AHLID scores and TAS-20 factors 2, 3 and TAS-20 total score were found. Regression analyses showed that TAS-20 factor 3, externally-oriented thinking (beta=-0.21, SE=0.02, p=0.017), and TAS-20 total score (beta=-0.18, SE=0.01, p=0.036) were significant predictors of AHLID level. Conclusion: The hypothesis that low oral health literacy is associated with alexithymia was supported. This finding proposes that alexithymia may be considered as a possible factor for low oral health literacy. However, the correlations are not strong, and the results should be regarded as a first step to provide evidence with additional research on this topic being needed.

  • 225.
    Steneberg, Pär
    et al.
    Umeå universitet, Medicinska fakulteten, Umeå centrum för molekylär medicin (UCMM).
    Lindahl, Emma
    Umeå universitet, Medicinska fakulteten, Umeå centrum för molekylär medicin (UCMM).
    Dahl, Ulf
    Umeå universitet, Medicinska fakulteten, Umeå centrum för molekylär medicin (UCMM).
    Lidh, Emmelie
    Umeå universitet, Medicinska fakulteten, Umeå centrum för molekylär medicin (UCMM).
    Straseviciene, Jurate
    Umeå universitet, Medicinska fakulteten, Umeå centrum för molekylär medicin (UCMM).
    Backlund, Fredrik
    Umeå universitet, Medicinska fakulteten, Umeå centrum för molekylär medicin (UCMM).
    Kjellkvist, Elisabet
    Umeå universitet, Medicinska fakulteten, Umeå centrum för molekylär medicin (UCMM).
    Berggren, Eva
    Lundberg, Ingela
    Bergqvist, Ingela
    Ericsson, Madelene
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Fysiologisk kemi.
    Eriksson, Björn
    Linde, Kajsa
    Westman, Jacob
    Edlund, Thomas
    Umeå universitet, Medicinska fakulteten, Umeå centrum för molekylär medicin (UCMM). Betagenon AB, Umeå, Sweden.
    Edlund, Helena
    Umeå universitet, Medicinska fakulteten, Umeå centrum för molekylär medicin (UCMM).
    PAN-AMPK activator O304 improves glucose homeostasis and microvascular perfusion in mice and type 2 diabetes patients2018Inngår i: JCI INSIGHT, ISSN 2379-3708, Vol. 3, nr 12, artikkel-id e99114Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    AMPK activated protein kinase (AMPK), a master regulator of energy homeostasis, is activated in response to an energy shortage imposed by physical activity and caloric restriction. We here report on the identification of PAN-AMPK activator O304, which - in diet-induced obese mice - increased glucose uptake in skeletal muscle, reduced beta cell stress, and promoted beta cell rest. Accordingly, O304 reduced fasting plasma glucose levels and homeostasis model assessment of insulin resistance (HOMA-IR) in a proof-of-concept phase IIa clinical trial in type 2 diabetes (T2D) patients on Metformin. T2D is associated with devastating micro-and macrovascular complications, and O304 improved peripheral microvascular perfusion and reduced blood pressure both in animals and T2D patients. Moreover, like exercise, O304 activated AMPK in the heart, increased cardiac glucose uptake, reduced cardiac glycogen levels, and improved left ventricular stroke volume in mice, but it did not increase heart weight in mice or rats. Thus, O304 exhibits a great potential as a novel drug to treat T2D and associated cardiovascular complications.

  • 226.
    Stenfors, Nikolai
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Hubinette, Anna
    Mid Sweden University.
    Lodin-Sundström, Angelica
    Mid Sweden University.
    Schagatay, Erika
    Mid Sweden University.
    Spleen contraction and erythrocyte release during exercised-induced hypoxia in patients with COPD2009Konferansepaper (Fagfellevurdert)
  • 227.
    Strigård, Karin
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Kirurgi.
    Clay, L.
    Stark, B.
    Gunnarsson, Ulf
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Kirurgi.
    Falk, P.
    Giant ventral hernia-relationship between abdominal wall muscle strength and hernia area2016Inngår i: BMC Surgery, ISSN 1471-2482, E-ISSN 1471-2482, Vol. 16, artikkel-id 50Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Symptoms arising from giant ventral hernia have been considered to be related to weakening of the abdominal muscles. The aim of this study was to investigate the relationship between the area of the abdominal wall defect and abdominal wall muscle strength measured by the validated BioDex system together with a back/ abdominal unit.

    Methods: Fifty-two patients with giant ventral hernia (> 10 cm wide) underwent CT scan, clinical measurement of hernia size and BioDex measurement of muscle strength prior to surgery. The areas of the hernia derived from CT scan and from clinical measurement were compared with BioDex forces in the modalities extension, flexion and isometric contraction. The Spearman rank test was used to calculate correlations between area, BMI, gender, age, and muscle strength.

    Result: The hernia area calculated from clinical measurements correlated to abdominal muscle strength measured with the Biodex for all modalities (p-values 0.015-0.036), whereas no correlation was seen with the area calculated by CT scan. No relationship was seen between BMI, gender, age and the area of the hernia.

    Discussion: The inverse correlation between BioDex abdominal muscle strength and clinically assessed hernia area, seen in all modalities, was so robust that it seems safe to conclude that the area of the hernia is an important determinant of the degree of loss of abdominal muscle strength. Results using hernia area calculated from the CT scan showed no such correlation and this would seem to concur with the results from a previous study by our group on patients with abdominal rectus diastasis. In that study, defect size assessed clinically, but not that measured by CT scan, was in agreement with the size of the diastasis measured intra-operatively.

    The point at which the area of a hernia begins to correlate with loss of abdominal wall muscle strength remains unknown since this study only included giant ventral hernias.

  • 228. Svedenhag, Jan
    et al.
    Larsson, Thomas P.
    Lindqvist, Per
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Klinisk fysiologi.
    Olsson, Arne
    Rythen Alder, Eva
    Individual reference values for 2D echocardiographic measurements. The Stockholm - Umeå Study2015Inngår i: Clinical Physiology and Functional Imaging, ISSN 1475-0961, E-ISSN 1475-097X, Vol. 35, nr 4, s. 275-282Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objectives: Improved reference values for 2D echocardiographic measurements are required, even when more recent echocardiographic technology is employed. In addition, it may be preferable to individualize reference values from age, gender and body characteristics of any subject. Design: A material of 180 healthy subjects was collected and investigated, aiming for an even distribution of sex and age (from 20 to 80years of age; the Stockholm material). For atrial areas, material from another 216 healthy subjects with similar sex and age distribution was added (the Umea material). The 2D measures determined were the left and right ventricular diameters in diastole, the left ventricular diameter in systole, the thickness of septum and posterior wall, the diameters of the aortic root (sinotubular junction) and the left atrium (all in parasternal view), together with the left and right ventricular diameters in diastole and left and right atrial areas in end-systole (apical four-chamber view). The width of the inferior vena cava (from subcostal view) was also determined. Results: Confidence intervals for females and males are presented for each of these measures. Multiple linear regression analyses with age, sex and measures of body characteristics as predictors were also performed, and for eight of the 12 measurements, such equations are presented. Conclusions: It is possible to obtain more highly individualized reference values for these cardiac dimensions, which may clinically be a better way of distinguishing pathological states from normal states.

  • 229.
    Säfström, Daniel
    Umeå universitet, Medicinsk fakultet, Integrativ medicinsk biologi.
    Sensorimotor transformations during grasping movements2006Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    ‘Sensorimotor transformations’ are processes whereby sensory information is used to generate motor commands. One example is the ‘visuomotor map’ that transforms visual information about objects to motor commands that activates various muscles during grasping movements. In the first study we quantified the relative impact (or ‘weighting’) of visual and haptic information on the sensorimotor transformation and investigated the principles that regulates the weighting process. To do this, we let subjects perform a task in which the object seen (visual object) and the object grasped (haptic object) were physically never the same. When the haptic object became larger or smaller than the visual object, subjects in the following trials automatically adapted their maximum grip aperture (MGA) when reaching for the object. The adaptation process was quicker and relied more on haptic information when the haptic objects increased in size than when they decreased in size. As such, sensory weighting is molded to avoid prehension error.

    In the second study we investigated the degree to which the visuomotor map could be modified. Normally, the relationship between the visual size of the object (VO) and the MGA can be expressed as a linear relationship, where MGA = a + b * VO. Our results demonstrate that subjects inter- and extrapolate in the visuomotor map (that is, they are reluctant to abandon the linear relationship) and that the offset (a) but not the slope (b) can be modified.

    In the third study, we investigated how a ‘new’ sensorimotor transformation can be established and modified. We therefore replaced the normal input of visual information about object size with auditory information, where the size of the object was log-linearly related to the frequency of a tone. Learning of an audiomotor map consisted of three distinct phases: during the first stage (~10-15 trials) there were no overt signs of learning. During the second stage there was a period of fast learning where the MGA became scaled to the size of the object until the third stage where the slope was constant.

    The purpose of the fourth study was to investigate the sensory basis for the aperture adaptation process. To do that, the forces acting between the fingertips and the object was measured as the subjects adapted. Our results indicate that information about when the fingers contacts the object, that is, the ‘timing’ of contact, is likely to be used by the CNS to encode an unexpected object size.

    Since injuries and disease can affect the sensorimotor transformations that controls the hand, knowledge about how these processes are established and modified may be used to develop techniques for sensory substitution and other rehabilitation strategies.

  • 230.
    Säfström, Daniel
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Fysiologi.
    Flanagan, J Randall
    Department of Psychology and Centre for Neuroscience Studies, Queen's University, Kingston, Ontario, Canada.
    Johansson, Roland S
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Fysiologi.
    Skill learning involves optimizing the linking of action phases2013Inngår i: Journal of Neurophysiology, ISSN 0022-3077, E-ISSN 1522-1598, Vol. 110, nr 6, s. 1291-1300Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Many manual tasks involve object manipulation and are achieved by an evolving series of actions, or action phases, recruited to achieve task subgoals. The ability to effectively link action phases is an important component of manual dexterity. However, our understanding of how the effective linking of sequential action phases develops with skill learning is limited. Here, we addressed this issue using a task in which participants applied forces to a handle to move a cursor on a computer screen to successively acquire visual targets. Target acquisition required actively holding the cursor within the target zone (hold phase) for a required duration, before moving to the next target (transport phase). If the transport phase was initiated prematurely, before the end of the required hold duration, participants had to return to the target to acquire it. The goal was to acquire targets as quickly as possible. Distinct visual and auditory sensory events marked goal completion of each action phase. During initial task performance, the transport phase was reactively triggered by sensory events signaling hold phase completion. However, with practice, participants learned to initiate the transport phase based on a prediction of the time of hold phase completion. Simulations revealed that participants learned to near-optimally compensate for temporal uncertainty, presumably related to estimation of time intervals and execution of motor commands, so as to reduce the average latency between the end of the required hold phase duration and the start of the transport phase, while avoiding an excess of premature exits.

  • 231.
    Säfström, Daniel
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Fysiologi.
    Johansson, Roland S
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Fysiologi.
    Flanagan, J Randall
    Department of Psychology and Centre for Neuroscience Studies, Queen’s University, Kingston, Ontario, Canada.
    Gaze behavior when learning to link sequential action phases in a manual task2014Inngår i: Journal of Vision, ISSN 1534-7362, E-ISSN 1534-7362, Vol. 14, nr 4Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Most manual tasks comprise a sequence of action phases. Skill acquisition in such tasks involves a transition from reactive control, whereby motor commands for the next phase are triggered by sensory events signaling completion of the current phase, to predictive control, whereby commands for the next phase are launched in anticipation of these events. Here we investigated gaze behavior associated with such learning. Participants moved a cursor to successively acquire visual targets, as quickly as possible, by actively keeping the cursor within the target zone (hold phase) for a required duration, before moving to the next target (transport phase). Distinct visual and auditory events marked completion of each phase and, with learning, the launching of the transport phase shifted from being reactively to predictively controlled. Initially, gaze was directed to the current target throughout the hold phase, allowing visual feedback control of the cursor position, and shifted to the next target in synchrony with the cursor. However, with learning, two distinct gaze behaviors emerged. Gaze either shifted to the next target well before the end of the hold phase, facilitating planning of the forthcoming cursor movement, or shifted to the next target after the cursor, enabling cursor exits to be monitored in central vision. These results suggest that, with learning, gaze behavior changes to support evolving task demands, and that people distribute different gaze behaviors across repetitions of the task.

  • 232.
    Teien, Dag
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Klinisk fysiologi.
    Assessment of aortic stenosis with special reference to Doppler ultrasound1986Doktoravhandling, med artikler (Annet vitenskapelig)
  • 233.
    Terao, Yasuo
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Fysiologi.
    Andersson, N E Micael
    Flanagan, J Randall
    Queen's University, Kingston, Ontario.
    Johansson, Roland S
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Fysiologi.
    Engagement of gaze in capturing targets for future sequential manual actions.2002Inngår i: Journal of Neurophysiology, ISSN 0022-3077, E-ISSN 1522-1598, Vol. 88, nr 4, s. 1716-25Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    We investigated the role of saccadic gaze fixations in encoding target locations for planning a future manual task consisting of a sequence of discrete target-oriented actions. We hypothesized that fixations of the individual targets are necessary for accurate encoding of target locations and that there is a transfer of sequence information from visual encoding to manual recall. Subjects viewed four targets presented at random positions on a screen. After various delays following target extinction, the subjects marked the remembered target locations on the screen with the tip of a hand-held stick. When the targets were presented simultaneously among distracting elements, the overall accuracy of marking increased with presentation time and total number of targets fixated because the subjects had to serially fixate the individual targets to locate them. Without distractors, the marking accuracy was similarly high regardless of duration of target presentation (0.25-8 s) and number of targets fixated; it was comparable to that with distractors when all four targets had been fixated. This indicates parallel encoding of target locations largely based on peripheral vision. Location memory was stable in these tasks over the delay periods investigated (0.5-8 s). With parallel encoding there was a "shrinkage" in the visuomotor transformation, i.e., the distances between the markings were systematically smaller than the corresponding inter-target distances. When the targets were presented sequentially without distractors, marking accuracy improved with the total number of targets fixated and shrinkage in the visuomotor transformation occurred only with parallel encoding, i.e., when subjects did not fixate the targets. In all experimental conditions for trials in which targets were fixated during encoding, there was little correspondence between the marking sequence and the sequence in which the targets were fixated. We conclude that subjects benefit from fixating targets for subsequent target-oriented manual actions when the targets are presented among distractors and when presented sequentially; when distinct targets are presented simultaneously against a blank background, they are efficiently encoded in parallel largely by peripheral vision.

  • 234.
    Theorin, Anna
    Umeå universitet, Medicinsk fakultet, Integrativ medicinsk biologi, Fysiologi.
    To select one hand while using both: neural mechanisms supporting flexible hand dominance in bimanual object manipulation2009Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    In daily activities, the brain regularly assigns different roles to the hands dependingon task and context. Yet, little is known about the underlying neural processes. Thiscertainly applies to how the brain, where each hemisphere primarily controls onehand, manages the between-hand coordination required in bimanual objectmanipulation. By using behavioral, neurophysiological and functional magneticresonance imaging techniques, the present thesis examines neural mechanisms thatsupport hand coordination during tasks where the two hands apply spatiotemporallycoupled but opposing forces for goal attainment, e.g., as when removing the cap froma bottle. Although the two hands seem to operate symmetrically in such tasks, Study Ishowed that one hand primarily acts while the other assists. Moreover, this roledifferentiation was found to be flexible with the brain appointing either hand asprime actor depending on the spatial congruency between hand forces and desiredmovement consequences. Accordingly, when we remove a cap from a bottle, the handthat grasps the cap, be it left or right depending on overall task constraints, isappointed as prime actor because the twist forces it generates are aligned with thegoal to remove the cap, while the other hand, holding the bottle, applies stabilizingforces in the opposite direction. Changes in hand assignments are caused by amidline shift of lateralized activity throughout the motor system, from distal handmuscles to corticospinal pathways and primary sensorimotor and cerebellar corticalareas (Study I). Although the bimanual actions examined involved both within- andbetween-hand coordination, Study II failed to reveal additional brain activity duringbimanual as compared to matching unimanual actions, except for the primarysensorimotor areas where subpopulations of neurons were preferentially engagedduring either bimanual or unimanual actions. Thus, dedicated neurons in the motorcortices might support critical bimanual coordinative operations. While imagingresults indicated that a mainly left-lateralized parietal-premotor network managedthe task irrespective of prime actor, premotor areas presumably established handassignment by allocating the lead either to the left or the right primary sensorimotorareas (Study I and II). Regarding the process of prime actor selection and hence thecontrol of these premotor networks, imaging results indicate a transitory involvementof prefrontal cortical areas (Study III). The detected areas belong to a networkconsidered critical for cognitive operations such as judgment and decision-making,and for evaluation of utility of actions, including conflict detection. The implicitselection of prime actor during bimanual tasks thus seems to be supported by corticalareas traditionally associated primarily with complex cognitive challenges.

  • 235.
    Theorin, Anna
    et al.
    Umeå universitet, Medicinsk fakultet, Integrativ medicinsk biologi, Fysiologi.
    Johansson, Roland
    Umeå universitet, Medicinsk fakultet, Integrativ medicinsk biologi, Fysiologi.
    Selection of prime actor in bimanual object manipulationManuskript (preprint) (Annet vitenskapelig)
  • 236.
    Theorin, Anna
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Fysiologi.
    Johansson, Roland S
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Fysiologi. Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI).
    Selection of prime actor in humans during bimanual object manipulation2010Inngår i: Journal of Neuroscience, ISSN 0270-6474, E-ISSN 1529-2401, Vol. 30, nr 31, s. 10448-10459Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    In bimanual object manipulation tasks, people flexibly assign one hand as a prime actor while the other assists. Little is known, however, about the neural mechanisms deciding the role assignment. We addressed this issue in a task in which participants moved a cursor to hit targets on a screen by applying precisely coupled symmetrical opposing linear and twist forces on a tool held freely between the hands. In trials presented in an unpredictable order, the action of either the left or the right hand was spatially congruent with the cursor movements, which automatically rendered the left or right hand the dominant actor, respectively. Functional magnetic resonance imaging indicated that the hand-selection process engaged prefrontal cortical areas belonging to an executive control network presumed critical for judgment and decision-making and to a salience network attributed to evaluation of utility of actions. Task initiation, which involved switching between task sets, had a superordinate role with reference to hand selection. Behavioral and brain imaging data indicated that participants initially expressed two competing action representations, matching either mapping rule, before selecting the appropriate one based on the consequences of the initial manual actions. We conclude that implicit processes engaging the prefrontal cortex reconcile selections among action representations that compete for the establishment of a dominant actor in bimanual object manipulation tasks. The representation selected is the one that optimizes performance by relying on the superior capacity of the brain to process spatial congruent, as opposed to noncongruent, mappings between manual actions and desired movement goals.

  • 237.
    Thomas, Christine K
    et al.
    University of Miami School of Medicine.
    Johansson, Roland S
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Fysiologi.
    Bigland-Ritchie, Brenda
    Yale University Medical School, New Haven, Connecticut.
    Incidence of F waves in single human thenar motor units.2002Inngår i: Muscle and Nerve, ISSN 0148-639X, E-ISSN 1097-4598, Vol. 25, nr 1, s. 77-82Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    F-wave generation, axon conduction velocities, and contractile properties were compared in 44 healthy individual human thenar motor units. Force and muscle action potentials were recorded when single motor axons were stimulated intraneurally about 10 cm proximal to the elbow. Each stimulus usually evoked only one electromyographic (EMG) potential. However, in seven units (16%), a single stimulus elicited an F wave in response to 1.7 +/- 1.6% (mean +/- SD) of the stimuli applied. Axon conduction velocity proximal to the site of stimulation was faster than distal conduction velocity (72.7 +/- 8.0 m/s versus 64.2 +/- 10.5 m/s). Distal conduction velocities, twitch forces, and contraction times were similar for units that did and did not generate F waves. Thus, no obvious subset of thenar motor units generated F waves. These results provide valuable baseline information on F waves that can be used to assess changes in axon conduction, motor unit contractile properties, and motoneuron excitability in disease.

  • 238.
    Thornell, Lars-Eric
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi.
    Gustafsson, Thomas
    Karolinska Institutet Karolinska University Hospital .
    Cederholm, Tommy
    Department of Public Health and Caring Uppsala Science Park Uppsala.
    Ulfhake, Brun
    Karolinska Institutet .
    "Sarcopenia" has earned its living2012Inngår i: Journal of applied physiology, ISSN 8750-7587, E-ISSN 1522-1601, Vol. 113, nr 4, s. 683-684Artikkel i tidsskrift (Fagfellevurdert)
  • 239.
    Trulsson, Mats
    et al.
    Karolinska Institutet.
    Johansson, Roland S
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Fysiologi.
    Orofacial mechanoreceptors in humans: encoding characteristics and responses during natural orofacial behaviors.2002Inngår i: Behavioural Brain Research, ISSN 0166-4328, E-ISSN 1872-7549, Vol. 135, nr 1-2, s. 27-33Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    We used microneurography to characterize stimulus-encoding properties of low-threshold mechanoreceptive afferents in human orofacial tissues. Signals were recorded from single afferents in the infraorbital, lingual and inferior alveolar nerves while localized, controlled, mechanical stimuli were delivered to the facial skin, lips, oral mucosa and teeth. We likewise analyzed activity in these afferents during orofacial behaviors such as speech, chewing and biting. The afferents in the soft tissues functionally resemble four types described in the human hand: hair follicle afferents, slowly adapting (SA) type I and type II afferents and fast adapting (FA) type I afferents. Afferents in the facial skin, lips and buccal mucosa respond not only to contact with environmental objects, but also to contact between the lips, changes in air pressure generated for speech sounds, and to facial skin and mucosa deformations that accompany lip and jaw movements associated with chewing and swallowing. Hence, in addition to exteroceptive information, these afferents provide proprioceptive information. In contrast, afferents terminating superficially in the tongue do not signal proprioceptive information about tongue movements in this manner. They only respond when the receptive field is brought into contact with other intraoral structures or objects, e.g. the teeth or food. All human periodontal afferents adapt slowly to maintained tooth loads. Populations of periodontal afferents encode information about both which teeth are loaded and the direction of forces applied to individual teeth. Most afferents exhibit a markedly curved relationship between discharge rate and force amplitude, featuring the highest sensitivity to changes in tooth load at low forces (below 1 N). Accordingly, periodontal afferents efficiently encode tooth load when subjects first contact, hold, and gently manipulate food by the teeth. In contrast, only a minority of the afferents encodes the rapid and strong force increase generated when biting through food. We conclude, that humans use periodontal afferent signals to control jaw actions associated with intraoral manipulation of food rather than exertion of jaw power actions.

  • 240.
    Ullén, Fredrik
    et al.
    Department of Woman and Child Health, Karolinska Institutet, SE-171 77 Stockholm, Sweden.
    Forsman, Lea
    Department of Woman and Child Health, Karolinska Institutet, SE-171 77 Stockholm, Sweden.
    Blom, Örjan
    Department of Woman and Child Health, Karolinska Institutet, SE-171 77 Stockholm, Sweden.
    Karabanov, Anke
    Department of Woman and Child Health, Karolinska Institutet, SE-171 77 Stockholm, Sweden.
    Madison, Guy
    Umeå universitet, Samhällsvetenskapliga fakulteten, Institutionen för psykologi.
    Intelligence and variability in a simple timing task share neural substrates in the prefrontal white matter2008Inngår i: Journal of Neuroscience, ISSN 0270-6474, EISSN 1529-2401, Vol. 28, nr 16, s. 4238-4243Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    General intelligence is correlated with the mean and variability of reaction time in elementary cognitive tasks, as well as with performance on temporal judgment and discrimination tasks. This suggests a link between the temporal accuracy of neural activity and intelligence. However, it has remained unclear whether this link reflects top-down mechanisms such as attentional control and cognitive strategies or basic neural properties that influence both abilities. Here, we investigated whether millisecond variability in a simple, automatic timing task, isochronous tapping, correlates with intellectual performance and, using voxel based morphometry, whether these two tasks share neuroanatomical substrates. Stability of tapping and intelligence were correlated and related to regional volume in overlapping right prefrontal white matter regions. These results suggest a bottom-up explanation of the link between temporal stability and intellectual performance, where more extensive prefrontal connectivity underlies individual differences in both variables.

  • 241.
    Vestergren, Peter
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Fysiologi.
    Nyberg, Lars
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Fysiologi.
    Test-potentiated encoding of paired associates as revealed by functional magnetic resonance imaging2013Inngår i: Journal of cognitive neuroscience, ISSN 0898-929X, E-ISSN 1530-8898, Vol. 25, nr Suppl., s. S113-S114Artikkel i tidsskrift (Annet vitenskapelig)
  • 242. Vimaleswaran, Karani Santhanakrishnan
    et al.
    Luan, Jian'an
    Andersen, Gitte
    Muller, Y Li
    Wheeler, Eleanor
    Brito, Ema C
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    O'Rahilly, Stephen
    Pedersen, Oluf
    Baier, Leslie J
    Knowler, William C
    Barroso, Inês
    Wareham, Nicholas J
    Loos, Ruth J F
    Franks, Paul W
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin. Medical Research Council, Epidemiology Unit, Institute of Metabolic Science, Cambridge, United Kingdom.
    The Gly482Ser genotype at the PPARGC1A gene and elevated blood pressure: a meta-analysis involving 13,949 individuals2008Inngår i: Journal of applied physiology, ISSN 8750-7587, E-ISSN 1522-1601, Vol. 105, nr 4, s. 1352-1358Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The protein encoded by the PPARGC1A gene is expressed at high levels in metabolically active tissues and is involved in the control of oxidative stress via reactive oxygen species detoxification. Several recent reports suggest that the PPARGC1A Gly482Ser (rs8192678) missense polymorphism may relate inversely with blood pressure. We used conventional meta-analysis methods to assess the association between Gly482Ser and systolic (SBP) or diastolic blood pressures (DBP) or hypertension in 13,949 individuals from 17 studies, of which 6,042 were previously unpublished observations. The studies comprised cohorts of white European, Asian, and American Indian adults, and adolescents from South America. Stratified analyses were conducted to control for population stratification. Pooled genotype frequencies were 0.47 (Gly482Gly), 0.42 (Gly482Ser), and 0.11 (Ser482Ser). We found no evidence of association between Gly482Ser and SBP [Gly482Gly: mean = 131.0 mmHg, 95% confidence interval (CI) = 130.5-131.5 mmHg; Gly482Ser mean = 133.1 mmHg, 95% CI = 132.6-133.6 mmHg; Ser482Ser: mean = 133.5 mmHg, 95% CI = 132.5-134.5 mmHg; P = 0.409] or DBP (Gly482Gly: mean = 80.3 mmHg, 95% CI = 80.0-80.6 mmHg; Gly482Ser mean = 81.5 mmHg, 95% CI = 81.2-81.8 mmHg; Ser482Ser: mean = 82.1 mmHg, 95% CI = 81.5-82.7 mmHg; P = 0.651). Contrary to previous reports, we did not observe significant effect modification by sex (SBP, P = 0.966; DBP, P = 0.715). We were also unable to confirm the previously reported association between the Ser482 allele and hypertension [odds ratio: 0.97, 95% CI = 0.87-1.08, P = 0.585]. These results were materially unchanged when analyses were focused on whites only. However, statistical evidence of gene-age interaction was apparent for DBP [Gly482Gly: 73.5 (72.8, 74.2), Gly482Ser: 77.0 (76.2, 77.8), Ser482Ser: 79.1 (77.4, 80.9), P = 4.20 x 10(-12)] and SBP [Gly482Gly: 121.4 (120.4, 122.5), Gly482Ser: 125.9 (124.6, 127.1), Ser482Ser: 129.2 (126.5, 131.9), P = 7.20 x 10(-12)] in individuals <50 yr (n = 2,511); these genetic effects were absent in those older than 50 yr (n = 5,088) (SBP, P = 0.41; DBP, P = 0.51). Our findings suggest that the PPARGC1A Ser482 allele may be associated with higher blood pressure, but this is only apparent in younger adults.

  • 243.
    Von Helversen, Bettina
    et al.
    University of Basel, Department of Psychology, Switzerland.
    Karlsson, Linnea
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Fysiologi.
    Mata, Rui
    Max Planck Institute for Human Development, Berlin, Germany.
    Wilke, Andreas
    Clarkson University, Department of Psychology, USA.
    Why does cue polarity information provide benefits in inference problems?: The role of strategy selection and knowledge of cue importance2013Inngår i: Acta Psychologica, ISSN 0001-6918, E-ISSN 1873-6297, Vol. 144, nr 1, s. 73-82Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Knowledge about cue polarity (i.e., the sign of a cue–criterion relation) seems to boost performance in a wide range of inference tasks. Knowledge about cue polarity information may enhance performance by increasing (1) the reliance on rule- relative to similarity-based strategies, and (2) explicit knowledge about the relative importance of cues. We investigated the relative contribution of these two mechanisms in a multiple-cue judgment task and a categorization task, which typically differ in the inference strategies they elicit and potentially the explicit task knowledge available to participants. In both tasks participants preferred rule-based relative to similarity-based strategies and had more knowledge about cue importance when cue polarity information was provided. Strategy selection was not related to increases in performance in the categorization task and could only partly explain increases in performance in the judgment task. In contrast, explicit knowledge about the importance of cues was related to better performance in both categorization and judgment independently of the strategy used. In sum, our results suggest that the benefits of receiving cue polarity information may span across tasks, such multiple-cue judgment and categorization, primarily by enhancing knowledge of relative cue importance.

  • 244. Von Walden, Ferdinand
    et al.
    Gantelius, Stefan
    Liu, Chang
    Borgström, Hanna
    Björk, Lars
    Gremark, Ola
    Stål, Per
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB).
    Nader, Gustavo A.
    Ponten, Eva
    Muscle contractures in patients with cerebral palsy and acquired brain injury are associated with extracellular matrix expansion, pro-inflammatory gene expression, and reduced rRNA synthesis2018Inngår i: Muscle and Nerve, ISSN 0148-639X, E-ISSN 1097-4598, Vol. 58, nr 2, s. 277-285Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Introduction: Children with cerebral palsy (CP) and acquired brain injury (ABI) commonly develop muscle contractures with advancing age. An underlying growth defect contributing to skeletal muscle contracture formation in CP/ABI has been suggested.

    Methods: The biceps muscles of children and adolescents with CP/ABI (n=20) and typically developing controls (n=10) were investigated. We used immunohistochemistry, quantitative real-time polymerase chain reaction, and Western blotting to assess gene expression relevant to growth and size homeostasis.

    Results: Classical pro-inflammatory cytokines and genes involved in extracellular matrix (ECM) production were elevated in skeletal muscle of children with CP/ABI. Intramuscular collagen content was increased and satellite cell number decreased and this was associated with reduced levels of RNA polymerase I transcription factors, 45s pre-rRNA and 28S rRNA.

    Discussion: The present study provides novel data suggesting a role for pro-inflammatory cytokines and reduced ribosomal production in the development/maintenance of muscle contractures, possibly underlying stunted growth and perimysial ECM expansion.

  • 245. Wagner, C A
    et al.
    Ott, Michael
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin.
    Klingel, K
    Beck, S
    Melzig, J
    Friedrich, B
    Wild, K N
    Bröer, S
    Moschen, I
    Albers, A
    Waldegger, S
    Tümmler, B
    Egan, M E
    Geibel, J P
    Kandolf, R
    Lang, F
    Effects of the serine/threonine kinase SGK1 on the epithelial Na(+) channel (ENaC) and CFTR: implications for cystic fibrosis.2001Inngår i: Cellular Physiology and Biochemistry, ISSN 1015-8987, E-ISSN 1421-9778, Vol. 11, nr 4Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Cystic fibrosis (CF) is characterized by impaired Cl(-) secretion and increased Na(+) reabsorption in several tissues including respiratory epithelium. Many CFTR mutations have been identified over the past years. However, only a poor correlation between the genotype and lung phenotype was found suggesting additional factors influencing the phenotype and course of the disease. The serine/threonine kinase SGK1 has recently been shown to stimulate the activity of the epithelial Na(+) channel ENaC. A variety of stimuli such as aldosterone, cell shrinkage, insulin or TGF-beta1 stimulate transcription and activate the SGK1 kinase. Here we further examined the effects of SGK1 on ENaC and CFTR which have mutual interactions and we analyzed sgk1 mRNA abundance in lung tissue from CF patients. Coexpression of CFTR and h-SGK1 in Xenopus oocytes increased ENaC currents as previously described. In addition CFTR mediated currents were also stimulated. h-SGK1 accelerated the expression of the amiloride sensitive Na(+)- current in Xenopus oocytes paralleled by increased ENaC-protein abundance in the oocyte membrane, an effect which was reversed by a h-SGK1(K127R) mutation lacking the ATP-binding site. The cation selectivity or Na(+) affinity were not affected. However, coexpression of h-SGK1 with ENaC altered the sensitivity of the Na(+)-channel to the inhibitors amiloride and triamterene. The inhibitory effect of CFTR expression on ENaC current was not affected by coexpression of h-SGK1 in Xenopus oocytes. Lung tissue from CF patients strongly expressed the serine/threonine kinase h-sgk1 which was not the case for non-CF lung tissue. Loss of CFTR function itself in a CF lung epithelial cell line did not increase SGK1 expression. In summary, enhanced expression of h-SGK1 in epithelial cells of CF-lung tissue may be a novel pathophysiological factor contributing to increased Na(+) channel activity and thus to increased Na(+) transport in CF.

  • 246.
    Waldenström, Anders
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Kardiologi.
    Ronquist, Gunnar
    Åberg, Anna-Maja
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Anestesiologi och intensivvård.
    Ahlstrom, Katarina
    Hauck, Philip
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Anestesiologi och intensivvård.
    Abrahamsson, Pernilla
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Anestesiologi och intensivvård.
    Johansson, Göran
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Anestesiologi och intensivvård.
    Biber, Björn
    Haney, Michael F.
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Anestesiologi och intensivvård.
    Ischaemic preconditioning reduces myocardial calcium overload in coronary-occluded pig hearts shown by continuous in vivo assessment using microdialysis2012Inngår i: Clinical Physiology and Functional Imaging, ISSN 1475-0961, E-ISSN 1475-097X, Vol. 32, nr 2, s. 133-138Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    During ischaemia, ATP depletion leads to insufficient fuelling for Na+/K+ ATPase, decreased electrochemical potential and increased influx of calcium ions. This study demonstrated a means to assess the effects of ischaemic preconditioning (IP) on the free intracellular Ca2+ pool during prolonged ischaemia. In a porcine myocardial ischaemia model, microdialysis (MD) was used for sampling of metabolic and injury markers in IP and non-IP (control) groups. 45Ca2+ was delivered in microperfusate locally to ischaemic myocardium, with distribution and uptake assessed by 45Ca2+ recovery in microdialysate. Cardiomyocytes in vitro were exposed to a Ca2+ ionophore and tested for 45Ca2+ uptake. An accentuated myocardial calcium ion influx (observed as an increased microdialysate 45Ca2+ recovery in the extracellular milieu) was noted in control pigs compared with IP pigs during ischaemia. Suspended cardiomyocytes preincubated with a Ca2+ ionophore to increase the intracellular calcium ion pool and subsequently incubated with 45Ca2+, displayed lower 45Ca2+ uptake in cells compared with control cells not exposed to the ionophore, corroborating the idea of a strong relationship between degree of intracellular calcium overload and microdialysate 45Ca2+ recovery. The ischaemic insult was differentially verified by metabolic and injury markers. We introduce an in vivo method for serial assessment of myocardial calcium overload during ischaemia, using a MD technique and 45Ca2+ inclusion. IP leads to relatively less calcium overload as assessed by this new method, and we interpret this to mean that reduction in calcium overload is an important part of the IP protective effect.

  • 247. Weiler, Jeffrey
    et al.
    Saravanamuttu, James
    Gribble, Paul L.
    Pruszynski, J. Andrew
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB). Brain and Mind Institute, Western University, London, Ontario, Canada; Department of Psychology, Western University, London, Ontario, Canada; Department of Physiology and Pharmacology, Western University, London, Ontario, Canada; Robarts Research Institute, Western University, London, Ontario, Canada.
    Coordinating long-latency stretch responses across the shoulder, elbow, and wrist during goal-directed reaching2016Inngår i: Journal of Neurophysiology, ISSN 0022-3077, E-ISSN 1522-1598, Vol. 116, nr 5, s. 2236-2249Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The long-latency stretch response (muscle activity 50-100 ms after a mechanical perturbation) can be coordinated across multiple joints to support goal-directed actions. Here we assessed the flexibility of such coordination and whether it serves to counteract intersegmental dynamics and exploit kinematic redundancy. In three experiments, participants made planar reaches to visual targets after elbow perturbations and we assessed the coordination of long-latency stretch responses across shoulder, elbow, and wrist muscles. Importantly, targets were placed such that elbow and wrist (but not shoulder) rotations could help transport the hand to the target-a simple form of kinematic redundancy. In experiment 1 we applied perturbations of different magnitudes to the elbow and found that long-latency stretch responses in shoulder, elbow, and wrist muscles scaled with perturbation magnitude. In experiment 2 we examined the trial-by-trial relationship between long-latency stretch responses at adjacent joints and found that the magnitudes of the responses in shoulder and elbow muscles, as well as elbow and wrist muscles, were positively correlated. In experiment 3 we explicitly instructed participants how to use their wrist to move their hand to the target after the perturbation. We found that long-latency stretch responses in wrist muscles were not sensitive to our instructions, despite the fact that participants incorporated these instructions into their voluntary behavior. Taken together, our results indicate that, during reaching, the coordination of long-latency stretch responses across multiple joints counteracts intersegmental dynamics but may not be able to exploit kinematic redundancy.

  • 248.
    Westberg, Karl-Gunnar
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Fysiologi.
    McFarland, David
    Kolta, Arlette
    Stohler, Christian
    Feine, Jocelyne
    Woda, Alain
    From movement to pain: a tribute to professor James P. Lund2008Inngår i: Journal of Orofacial Pain, ISSN 1064-6655, E-ISSN 1945-3396, Vol. 22, nr 4, s. 297-306Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    This tribute article to Professor James P. Lund stems from 6 of the presentations delivered at the July 1, 2008, symposium that honored 3 "giants" in orofacial neuroscience: B. J. Sessle, A. G. Hannam, and J. P. Lund. It was noted that soon after his training as a dentist in Australia, Jim Lund became interested in research. At the time he decided to do a PhD, there was a lot of discussion about how rhythmic movements were programmed. The early belief, based on Sherrington's studies of motor systems, was that these movements were simply an alternating series of reflexes. In the late 1960s and early 1970s, some still shared this belief, whereas others favored Graham Brown's hypothesis that repetitive movements were centrally programmed and did not depend on reflexes triggered by sensory inputs. There was no strong evidence then for either scenario except for the rhythmic movements of respiration. Lund's pioneering work during his PhD proved the existence of a central pattern generator (CPG) for mastication in the brainstem. Since then he has been interested in understanding how CPGs function and how sensory feedback works to adjust the motor patterns that they produce. Sections in this tribute article to Lund are written by some of his close collaborators and reflect the evolution of his work throughout the years. The first 4 presentations in this article (by K.-G. Westberg, D. McFarland, A. Kolta, and C. Stohler) highlight various aspects of these interests, and the final 2 presentations (by J. Feine and A. Woda) focus especially on clinical aspects of Lund's interests. The last section of this article is a final commentary from Professor Lund.

  • 249.
    Westberg, Karl-Gunnar
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Fysiologi.
    Scott, G
    Université de Montréal, McGill University, Montréal.
    Olsson, Kurt
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Fysiologi.
    Lund, J P
    Université de Montréal, McGill University, Montréal.
    Discharge patterns of neurons in the medial pontobulbar reticular formation during fictive mastication in the rabbit2001Inngår i: European Journal of Neuroscience, ISSN 0953-816X, E-ISSN 1460-9568, Vol. 14, nr 10, s. 1709-1718Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    In this study, we describe functional characteristics of neurons forming networks generating oral ingestive motor behaviours. Neurons in medial reticular nuclei on the right side of the brainstem between the trigeminal and hypoglossal motor nuclei were recorded in anaesthetized and paralysed rabbits during two types of masticatory-like motor patterns induced by electrical stimulation of the left (contralateral) or right (ipsilateral) cortical masticatory areas. Sixty-seven neurons in nucleus reticularis pontis caudalis (nPontc), nucleus reticularis parvocellularis (nParv), and nucleus reticularis gigantocellularis (Rgc) were studied. These were classified as phasic or tonic depending on their firing pattern during the fictive jaw movement cycle. Phasic neurons located in the dorsal part of nPontc were active during the jaw opening phase, whilst those in dorsal nParv tended to fire during the closing phase. In most neurons, burst duration and firing frequency changed between the two motor patterns, but there was little change in phase of firing. Tonic units were mainly recorded in the ventral half of nPontc, and at the junction between Rgc and caudal nParv. Cortical inputs with short latency from the contralateral masticatory area were more frequent in phasic (82%) than tonic (44%) neurons, whilst inputs from the ipsilateral cortex were equal in the two subgroups (57% and 56%). Phasic neurons had significantly shorter mean contralateral than ipsilateral cortical latencies, whilst there was no difference among tonic neurons. Intra- and perioral primary afferent inputs activated both types of neurons at oligo-synaptic latencies. Our results show that subpopulations of neurons in medial reticular nuclei extending from the caudal part of the trigeminal motor nucleus to the rostral third of the hypoglossal motor nucleus are active during the fictive masticatory motor behaviour. Unlike masticatory neurons in the lateral tegmentum, the medial subpopulations are spatially organized according to discharge pattern.

  • 250.
    Wiesinger, Birgitta
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för odontologi.
    Häggman-Henrikson, Birgitta
    Umeå universitet, Medicinska fakulteten, Institutionen för odontologi.
    Wänman, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för odontologi. Wänman.
    Lindkvist, Marie
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Hellström, F
    Jaw-opening accuracy is not affected by masseter muscle vibration in healthy men2014Inngår i: Experimental Brain Research, ISSN 0014-4819, E-ISSN 1432-1106, Vol. 232, nr 11, s. 3501-3508Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    There is a functional integration between the jaw and neck regions with head extension-flexion movements during jaw-opening/closing tasks. We recently reported that trigeminal nociceptive input by injection of hypertonic saline into the masseter muscle altered this integrated jaw-neck function during jaw-opening/closing tasks. Thus, in jaw-opening to a predefined position, the head-neck component increased during pain. Previous studies have indicated that muscle spindle stimulation by vibration of the masseter muscle may influence jaw movement amplitudes, but the possible effect on the integrated jaw-neck function is unknown. The aim of this study was to investigate the effect of masseter muscle vibration on jaw-head movements during a continuous jaw-opening/closing task to a target position. Sixteen healthy men performed two trials without vibration (Control) and two trials with bilateral masseter muscle vibration (Vibration). Movements of the mandible and the head were registered with a wireless three-dimensional optoelectronic recording system. Differences in jaw-opening and head movement amplitudes between Control and Vibration, as well as achievement of the predefined jaw-opening target position, were analysed with Wilcoxon's matched pairs test. No significant group effects from vibration were found for jaw or head movement amplitudes, or in the achievement of the target jaw-opening position. A covariation between the jaw and head movement amplitudes was observed. The results imply a high stability for the jaw motor system in a target jaw-opening task and that this task was achieved with the head-neck and jaw working as an integrated system.

23456 201 - 250 of 266
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