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  • Bentzer, Peter, et al. (författare)
  • Supersensitivity in rat micro-arteries after short-term denervation
  • 1997
  • Ingår i: Acta Physiologica Scandinavica. - Wiley-Blackwell. - 0001-6772. ; 161:2, s. 125-133
  • Tidskriftsartikel (refereegranskat)abstract
    • Contractile responses to phenylephrine and high-K+ were investigated in vitro in microvascular preparations from the rat medial plantar artery, a branch from the saphenous artery, obtained after short-term denervation in vivo. Two groups of animals were studied: (1) animals undergoing surgical resection of the saphenous nerve, and (2) animals undergoing surgical resection of both the sciatic and saphenous nerves. The animals were operated on one side only. Microvascular preparations (diameter about 325 microns) were obtained 10 days after surgery. Vessels from the non-operated side served as controls. Immunocytochemistry showed a decreased number of both neuropeptide Y (NPY) and calcitonin gene-related peptide (CGRP) immunoreactive nerve fibres in vessels after resection of the saphenous nerve only. Resection of both the saphenous and the sciatic nerve caused a complete loss of immunoreactive nerve fibres. Mechanical measurements were performed using a wire myograph. In vessels subjected to resection of the saphenous nerve the sensitivity to phenylephrine was similar to controls. Vessels denervated by resection of both the saphenous and sciatic nerves showed significant increases in phenylephrine and potassium sensitivity. When depolarized in high-K+ solution the denervated vessels showed an increased sensitivity to extracellular Ca2+. The results show that complete short-term denervation of the rat medial plantar artery in vivo causes a pronounced supersensitivity in the vascular smooth muscle. The supersensitivity appears not to be restricted to the sympathetic alpha-receptors but also associated with changes in the cellular excitation-contraction coupling. Such altered reactivity of the vascular smooth muscle may contribute to vascular disturbances observed in vivo after nerve damage or surgical denervation.
  • Abramsson, Alexandra, 1973-, et al. (författare)
  • The zebrafish amyloid precursor protein-b is required for motor neuron guidance and synapse formation.
  • 2013
  • Ingår i: Developmental biology. - 1095-564X. ; 381:2, s. 377-88
  • Tidskriftsartikel (refereegranskat)abstract
    • The amyloid precursor protein (APP) is a transmembrane protein mostly recognized for its association with Alzheimer's disease. The physiological function of APP is still not completely understood much because of the redundancy between genes in the APP family. In this study we have used zebrafish to study the physiological function of the zebrafish APP homologue, appb, during development. We show that appb is expressed in post-mitotic neurons in the spinal cord. Knockdown of appb by 50-60% results in a behavioral phenotype with increased spontaneous coiling and prolonged touch-induced activity. The spinal cord motor neurons in these embryos show defective formation and axonal outgrowth patterning. Reduction in Appb also results in patterning defects and changed density of pre- and post-synapses in the neuromuscular junctions. Together, our data show that development of functional locomotion in zebrafish depends on a critical role of Appb in the patterning of motor neurons and neuromuscular junctions.
  • Andersson, Daniel P., et al. (författare)
  • Omentectomy in addition to gastric bypass surgery and influence on insulin sensitivity : A randomized double blind controlled trial
  • 2014
  • Ingår i: Clinical Nutrition. - 0261-5614 .- 1532-1983. ; 33:6, s. 991-996
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>Background &amp; aims: Accumulation of visceral adipose tissue is associated with insulin resistance and cardio-vascular disease. The aim of this study was to elucidate whether removal of a large amount of visceral fat by omentectomy in conjunction with Roux en-Y gastric bypass operation (RYGB) results in enhanced improvement of insulin sensitivity compared to gastric bypass surgery alone. Methods: Eighty-one obese women scheduled for RYGB were included in the study. They were randomized to RYGB or RYGB in conjunction with omentectomy. Insulin sensitivity was measured by hyperinsulinemic euglycemic clamp before operation and sixty-two women were also reexamined 2 years post-operatively. The primary outcome measure was insulin sensitivity and secondary outcome measures included cardio-metabolic risk factors. Results: Two-year weight loss was profound but unaffected by omentectomy. Before intervention, there were no clinical or metabolic differences between the two groups. The difference in primary outcome measure, insulin sensitivity, was not significant between the non-omentectomy (6.7 +/- 1.6 mg/kg body weight/minute) and omentectomy groups (6.6 +/- 1.5 mg/kg body weight/minute) after 2 years. Nor did any of the cardio-metabolic risk factors that were secondary outcome measures differ significantly. Conclusion: Addition of omentectomy to gastric bypass operation does not give an incremental effect on long term insulin sensitivity or cardio-metabolic risk factors. The clinical usefulness of omentectomy in addition to gastric bypass operation is highly questionable.</p>
  • Arner, Anders, et al. (författare)
  • Calcium transients and the effect of a photolytically released calcium chelator during electrically induced contractions in rabbit rectococcygeus smooth muscle
  • 1998
  • Ingår i: Biophysical Journal. - Cell Press. - 1542-0086. ; 75:4, s. 1895-1903
  • Tidskriftsartikel (refereegranskat)abstract
    • Intracellular Ca2+ was determined with the fura-2 technique during electrically induced contractions in the rabbit rectococcygeus smooth muscle at 22 degreesC. The muscles were electrically activated to give short, reproducible contractions. Intracellular [Ca2+] increased during activation; the increase in [Ca2+] preceded force development by approximately 2 s. After cessation of stimulation Ca2+ fell, preceding the fall in force by approximately 4 s. The fluorescence properties of fura-2 were determined with time-resolved spectroscopy using synchrotron light at the MAX-storage ring, Lund, Sweden. The fluorescence decay of free fura-2 was best described by two exponential decays (time constants approximately 0.5 and 1.5 ns) at low Ca2+ (pCa 9). At high Ca2+ (pCa 4.5), fluorescence decay became slower and could be fitted by one exponential decay (1.9 ns). Time-resolved anisotropy of free fura-2 was characteristic of free rotational motion (correlation time 0.3 ns). Motion of fura-2 could be markedly inhibited by high concentrations of creatine kinase. Time-resolved spectroscopy measurements of muscle fibers loaded with fura-2 showed that the fluorescence lifetime of the probe was longer, suggesting an influence of the chemical environment. Anisotropy measurements revealed, however, that the probe was mobile in the cells. The Ca2+-dependence of contraction and relaxation was studied using a photolabile calcium chelator, diazo-2, which could be loaded into the muscle cells in a similar manner as fura-2. Photolysis of diazo-2 leads to an increase in its Ca2+-affinity and a fall in free Ca2+. When muscles that had been loaded with diazo-2 were illuminated with UV light flashes during the rising phase of contraction, the rate of contraction became slower, suggesting a close relation between intracellular Ca2+ and the cross-bridge interaction. In contrast, photolysis during relaxation did not influence the rate of force decay, suggesting that relaxation of these contractions is not determined by the rate of Ca2+ removal or due to an increased Ca2+ sensitivity, but instead is limited by other processes such as deactivation by dephosphorylation or detachment of tension-bearing cross-bridges, possibly regulated by thin filament systems.
  • Arner, Anders, et al. (författare)
  • Cross-bridge cycling in smooth muscle: a short review
  • 1998
  • Ingår i: Acta Physiologica Scandinavica. - Wiley-Blackwell. - 0001-6772. ; 164:4, s. 363-372
  • Tidskriftsartikel (refereegranskat)abstract
    • This review is focused on the cross-bridge interaction of the organized contractile system of smooth muscle fibres. By using chemically skinned preparations the different enzymatic reactions of actin-myosin interaction have been associated with mechanical events. A rigor state has been identified in smooth muscle and the binding of ATP causes dissociation of rigor cross-bridges at rates slightly slower than those in skeletal muscle, but fast enough not to be rate-limiting for cross-bridge turn over in the muscle fibre. The release of inorganic phosphate (Pi) is associated with force generation, and this process is not rate-limiting for maximal shortening velocity (Vmax) in the fully activated muscle. The binding of ADP to myosin is strong in the smooth muscle contractile system, a property that might be associated with the generally slow cross-bridge turn over. Both force and Vmax are modulated by the extent of myosin light chain phosphorylation. Low levels of activation are considered to be associated with the recruitment of slowly cycling dephosphorylated cross-bridges which reduces shortening velocity. The attachment of these cross-bridge states in skinned smooth muscles can be regulated by cooperative mechanisms and thin filament associated systems. Smooth muscles exhibit a large diversity in their Vmax and the individual smooth muscle tissue can alter its Vmax under physiological conditions. The diversity and the long-term modulation of phenotype are associated with changes in myosin heavy and light chain isoform expression.
  • Arner, Anders, et al. (författare)
  • Intracellular calcium in hypertrophic smooth muscle from rat urinary bladder
  • 2007
  • Ingår i: Scandinavian Journal of Urology and Nephrology. - Taylor & Francis. - 0036-5599. ; 41:4, s. 270-277
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective. To explore whether infravesical outlet obstruction is associated with alterations in calcium activation of detrusor smooth muscle. Material and methods. Outlet obstruction was created by partial ligature of the urethra in female rats. Western blotting was performed using an antibody against the cytoplasmatic region of the alpha(1c) subunit of the L- type Ca2(+) channel. Intracellular calcium was measured using Fura-2 in detrusors that had been obstructed for 10 days and activated by high K+ concentrations at different extracellular Ca2(+) concentrations. The rate of force development after rapid opening of L- type Ca2(+) channels was measured in contractions initiated by flash photolysis of nifedipine in Ca2(+) containing depolarizing solution. Results. Bladder weight increased from 6293 to 254943 mg after 10 days of obstruction. Expression of the alpha(1c) subunit increased after 3 days and continued to increase until it was about fourfold greater after 10 days; however, it had not increased further at 6 weeks. This change was reversible after removal of obstruction. Activation with K+ produced a stable force at different extracellular Ca2(+) concentrations, with no difference in response between controls and rats that had been obstructed for 10 days. Intracellular Ca2(+) concentrations were lower in the obstructed group, showing that the calcium sensitivity of the contraction force had increased. The delay between the opening of L- type channels and the onset of contraction was longer in obstructed detrusors. Conclusions. Growth of detrusor muscle following obstruction is accompanied by attenuated calcium transients following activation, despite upregulation of L- type Ca2(+) channels. The Ca2(+) sensitivity of contraction was increased in obstructed detrusors. We suggest that the decreased surface: volume ratio in hypertrophic smooth muscle cells is partly involved in the lowered Ca2(+) transients. The increases in L- type calcium channels and in calcium sensitivity may be compensatory mechanisms.
  • Arner, Anders, et al. (författare)
  • Smooth, slow and smart muscle motors.
  • 2003
  • Ingår i: Journal of Muscle Research and Cell Motility. - Springer. - 0142-4319. ; 24:2-3, s. 165-173
  • Tidskriftsartikel (refereegranskat)abstract
    • Smooth muscle is a slow and economical muscle with a large variability in contractile properties. This review describes results regarding the relation between expression of myosin isoforms and the contraction of smooth muscle. The focus of the review is on studies of the organised contractile system in the smooth muscle tissue. The role of the myosin heavy chain variants formed by alternative splicing in the myosin heavy chain tail (SM1, SM2 isoforms) and head (SM-A SM-B isoforms) regions, as well as the role of essential light chains (LC17a, LC17b isoforms) for the variability of contractile properties are discussed. Smooth muscle also has the ability to alter its contractile properties in response to altered functional demands in vivo, e.g. during hypertrophic growth of urinary bladder, intestine, uterus and vessels and in response to altered hormone levels. These alterations involve changes in myosin expression and altered contractile kinetics. Non-muscle myosin has been shown to have a contractile function in some smooth muscle tissues and recent data on the kinetic properties of non-muscle myosin filaments in smooth muscle tissue are described.
  • Arner, Peter, et al. (författare)
  • Variations in the size of the major omentum are primarily determined by fat cell number
  • 2013
  • Ingår i: Journal of Clinical Endocrinology and Metabolism. - The Endocrine Society. - 0021-972X .- 1945-7197. ; 98:5, s. E897-E901
  • Tidskriftsartikel (refereegranskat)abstract
    • <p><strong>OBJECTIVE:</strong> Accumulation of visceral adipose tissue (VAT) is strongly linked to insulin resistance. Variations in the size of any adipose depot are determined by alterations in adipocyte volume and/or number. The individual contribution of each of the latter factors was determined in the major omentum, a fully resectable VAT depot.</p><p><strong>SUBJECTS:</strong> Total removal of the major omentum (omentectomy) was performed in conjunction with bariatric surgery in 55 obese patients. Tissue weight as well as mean adipocyte size and number in the omentum were determined. In subgroups, total VAT was estimated by computerized tomography (n = 17) or dual-energy x-ray absorptiometry (n = 34).</p><p><strong>RESULTS:</strong> The weight of the major omentum (on average 0.6 kg) correlated significantly with total VAT mass estimated by computerized tomography or dual-energy x-ray absorptiometry (r = 0.48-0.7; P &lt; .01). Omental weight in relation to total body fat correlated with several features of the metabolic syndrome and inversely with serum-leptin (P &lt; .001). Mean adipocyte size and total adipocyte number correlated strongly with omental weight (r = 0.6-0.8; P &lt; .0001), irrespective of body mass index and total body fat mass, and accounted almost in total for interindividual variations in omental size. However, stepwise regression analysis demonstrated that adipocyte number was significantly (P &lt; .0001) more important (62%) than adipocyte size (35%).</p><p><strong>CONCLUSION:</strong> The size of the major omentum is representative for VAT mass and correlates with a pernicious metabolic profile. Variations in omental weight are primarily determined by adipocyte number and to a lesser degree by adipocyte size, suggesting that increased VAT mass in obesity is predominantly dependent on adipocyte proliferation.</p>
  • Balogh, Johanna, et al. (författare)
  • Desmin filaments influence myofilament spacing and lateral compliance of slow skeletal muscle fibres.
  • 2005
  • Ingår i: Biophysical Journal. - Cell Press. - 1542-0086. ; 88:2, s. 1156-1165
  • Tidskriftsartikel (refereegranskat)abstract
    • Intermediate filaments composed of desmin interlink Z-disks and sarcolemma in skeletal muscle. Depletion of desmin results in lower active stress of smooth, cardiac, and skeletal muscles. Structural functions of intermediate filaments in fast (psoas) and slow (soleus) skeletal muscle were examined using x-ray diffraction on permeabilized muscle from desmin-deficient mice (Des–/–) and controls (Des+/+). To examine lateral compliance of sarcomeres and cells, filament distances and fiber width were measured during osmotic compression with dextran. Equatorial spacing (x-ray diffraction) of contractile filaments was wider in soleus Des–/– muscle compared to Des+/+, showing that desmin is important for maintaining lattice structure. Osmotic lattice compression was similar in Des–/– and Des+/+. In width measurements of single fibers and bundles, Des–/– soleus were more compressed by dextran compared to Des+/+, showing that intermediate filaments contribute to whole-cell compliance. For psoas fibers, both filament distance and cell compliance were similar in Des–/– and Des+/+. We conclude that desmin is important for stabilizing sarcomeres and maintaining cell compliance in slow skeletal muscle. Wider filament spacing in Des–/– soleus cannot, however, explain the lower active stress, but might influence resistance to stretch, possibly minimizing stretch-induced cell injury.
  • Balogh, Johanna, et al. (författare)
  • Hearts from mice lacking desmin have a myopathy with impaired active force generation and unaltered wall compliance.
  • 2002
  • Ingår i: Cardiovascular Research. - Elsevier. - 1755-3245. ; 53:2, s. 439-450
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE: Desmin intermediate filaments are key structures in the cytoskeleton of cardiac muscle. Since they are associated with Z-discs and intercalated discs, they may have a role in sarcomere alignment or force transmission. We have explored the mechanical function of the desmin filaments in the cardiac wall by comparing desmin-deficient (Des-/-) and wild-type (Des+/+) mice. METHODS: The Langendorff technique was used to examine the contractility of the whole heart. Rate of force generation, Ca(2+)-sensitivity and force per cross-sectional area were measured in skinned ventricle muscle preparations. RESULTS: Des-/- mice have a cardiomyopathy with increased heart weight. Diastolic pressure was increased at all filling volumes in the Des-/- group. Since passive wall stress (i.e. force per area) was unchanged, the alteration in diastolic pressure is a consequence of the thicker ventricle wall. Developed pressure, rate of pressure increase and developed wall stress were significantly reduced, suggesting that active force generation of the contractile apparatus is reduced in Des-/-. Concentrations of actin and myosin in the ventricle were unaltered. Measurements in skinned muscle preparations showed a lower active force development with unaltered Ca(2+)-sensitivity and rate of tension development. CONCLUSION: It is suggested that the intermediate filaments have a role in active force generation of cardiac muscle, possibly by supporting sarcomere alignment or force transmission. The desmin filaments do not contribute the passive elasticity of the ventricle wall. Des-/- mice provide a model for genetic cardiomyopathy where the main factor contributing to altered cardiac performance is a decrease in active force generation, possibly in combination with a loss of functional contractile units.
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