umu.sePublications
Change search
Refine search result
1 - 42 of 42
CiteExportLink to result list
Permanent link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Rows per page
  • 5
  • 10
  • 20
  • 50
  • 100
  • 250
Sort
  • Standard (Relevance)
  • Author A-Ö
  • Author Ö-A
  • Title A-Ö
  • Title Ö-A
  • Publication type A-Ö
  • Publication type Ö-A
  • Issued (Oldest first)
  • Issued (Newest first)
  • Created (Oldest first)
  • Created (Newest first)
  • Last updated (Oldest first)
  • Last updated (Newest first)
  • Disputation date (earliest first)
  • Disputation date (latest first)
  • Standard (Relevance)
  • Author A-Ö
  • Author Ö-A
  • Title A-Ö
  • Title Ö-A
  • Publication type A-Ö
  • Publication type Ö-A
  • Issued (Oldest first)
  • Issued (Newest first)
  • Created (Oldest first)
  • Created (Newest first)
  • Last updated (Oldest first)
  • Last updated (Newest first)
  • Disputation date (earliest first)
  • Disputation date (latest first)
Select
The maximal number of hits you can export is 250. When you want to export more records please use the Create feeds function.
  • 1.
    Ahmadi, Mahboobah
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy. Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Liu, Jing-Xia
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Brännström, Thomas
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Andersen, Peter M
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurology.
    Stål, Per
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Pedrosa-Domellöf, Fatima
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Human extraocular muscles in ALS2010In: Investigative Ophthalmology and Visual Science, ISSN 0146-0404, E-ISSN 1552-5783, Vol. 51, no 7, p. 3494-3501Article in journal (Refereed)
    Abstract [en]

    PURPOSE. To investigate the general morphology, fiber type content, and myosin heavy chain (MyHC) composition of extraocular muscles (EOMs) from postmortem donors with amyotrophic lateral sclerosis (ALS) and to evaluate whether EOMs are affected or truly spared in this disease. METHODS. EOM and limb muscle samples obtained at autopsy from ALS donors and EOM samples from four control donors were processed for immunohistochemistry with monoclonal antibodies against distinct MyHC isoforms and analyzed by SDS-PAGE. In addition, hematoxylin and eosin staining and nicotinamide tetrazolium reductase (NADH-TR) activity were studied. RESULTS. Wide heterogeneity was observed in the appearance of the different EOMs from each single donor and between donors, irrespective of ALS type or onset. Pathologic morphologic findings in ALS EOMs included presence of atrophic and hypertrophic fibers, either clustered in groups or scattered; increased amounts of connective tissue; and areas of fatty replacement. The population of fibers stained with anti-MyHCslow tonic was smaller than that of MyHCIpositive fibers and was mostly located in the orbital layer in most of the ALS EOM samples, whereas an identical staining pattern for both fiber populations was observed in the control specimens. MyHCembryonic was notably absent from the ALS EOMs. CONCLUSIONS. The EOMs showed signs of involvement with altered fiber type composition, contractile protein content, and cellular architecture. However, when compared to the limb muscles, the EOMs were remarkably preserved. EOMs are a useful model for the study of the pathophysiology of ALS.

  • 2.
    Dahl, Morten
    et al.
    Institute of Sports Medicine, Department 8, Bispebjerg Hospital and Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark.
    Hansen, Philip
    Institute of Sports Medicine, Department 8, Bispebjerg Hospital and Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark.
    Stål, Per
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Edmundsson, David
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Orthopaedics.
    Magnusson, S. Peter
    Institute of Sports Medicine, Department 8, Bispebjerg Hospital and Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark.
    Stiffness and thickness of Fascia do not explain chronic exertional compartment syndrome2011In: Clinical Orthopaedics and Related Research, ISSN 0009-921X, E-ISSN 1528-1132, Vol. 469, no 12, p. 3495-3500Article in journal (Refereed)
    Abstract [en]

    Background   Chronic exertional compartment syndrome is diagnosed based on symptoms and elevated intramuscular pressure and often is treated with fasciotomy. However, what contributes to the increased intramuscular pressure remains unknown.

    Questions/purposes   We investigated whether the stiffness or thickness of the muscle fascia could help explain the raised intramuscular pressure and thus the associated chronic compartment syndrome symptoms.

    Patients and Methods   We performed plain radiography, bone scan, and intramuscular pressure measurement to diagnose chronic compartment syndrome and to exclude other disorders. Anterior tibialis muscle fascial biopsy specimens from six healthy individuals, 11 patients with chronic compartment syndrome, and 10 patients with diabetes mellitus and chronic compartment syndrome were obtained. Weight-normalized fascial stiffness was assessed mechanically in a microtensile machine, and fascial thickness was analyzed microscopically.

    Results   Mean fascial stiffness did not differ between healthy individuals (0.120 N/mg/mm; SD, 0.77 N/mg/mm), patients with chronic compartment syndrome (0.070 N/mg/mm; SD, 0.052 N/mg/mm), and patients with chronic compartment syndrome and diabetes (0.097 N/mg/mm; SD, 0.073 N/mg/mm). Similarly, no differences in fascial thickness were present. There was a negative correlation between fascial stiffness and intramuscular pressure in the patients with chronic compartment syndrome and diabetes.

    Conclusions   The lack of difference in fascial thickness and stiffness in patients with chronic compartment syndrome and patients with chronic compartment syndrome and diabetes compared with healthy individuals suggests structural and mechanical properties are unlikely to explain chronic compartment syndrome. To prevent chronic exertional compartment syndrome, it is necessary to address aspects other than the muscle fascia.

  • 3.
    Edmundsson, David S.
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences.
    Toolanen, Goran L.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences.
    Stål, Per S.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Muscle changes in patients with diabetes and chronic exertional compartment syndrome before and after treatment with fasciotomy2018In: Muscle and Nerve, ISSN 0148-639X, E-ISSN 1097-4598, Vol. 57, no 2, p. 229-239Article in journal (Refereed)
    Abstract [en]

    Introduction: Muscle changes in patients with diabetes and lower leg pain due to chronic exertional compartment syndrome (CECS) were investigated before and after fasciotomy. Methods: The tibialis anterior muscle was analyzed with histochemical and morphological techniques in 7 patients with diabetes and CECS before fasciotomy and in 5 of them 1 year after fasciotomy. Nondiabetic patients with CECS and healthy participants served as references. Results: Before treatment, walking distance until occurrence of pain was limited (<0.2 km). Intramuscular pressure was significantly higher than in reference participants. Muscle analysis showed changes pathognomonic for neuropathy and myopathy and a restricted capillary network, with significantly more severe changes in the muscles of patients with diabetes than in the muscles of nondiabetic patients. Treatment with fasciotomy improved clinical signs, increased walking ability, and reduced muscle abnormalities, but muscle capillarization remained low. Discussion: Patients with diabetes and CECS have distinct pathological changes in affected muscles. Pressure-relieving fasciotomy triggers a regenerative response in the muscle tissue but not in the capillary bed.

  • 4.
    Edmundsson, David
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences.
    Toolanen, Göran
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Orthopaedics.
    Stål, Per
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Muscle changes in diabetics with chronic compartment syndromeManuscript (preprint) (Other academic)
  • 5.
    Edmundsson, David
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Orthopaedics.
    Toolanen, Göran
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Orthopaedics.
    Thornell, Lars-Eric
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Stål, Per
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Evidence for low muscle capillary supply as a pathogenic factor in chronic compartment syndrome2010In: Scandinavian Journal of Medicine and Science in Sports, ISSN 0905-7188, E-ISSN 1600-0838, Vol. 20, no 6, p. 805-813Article in journal (Refereed)
    Abstract [en]

    There is a paucity of data regarding the pathogenesis of chronic exertional compartment syndrome (CECS), its consequences for the muscles and the effects of treatment with fasciotomy. We analyzed biopsies from the tibialis anterior muscle, from nine patients, obtained during a decompressing fasciotomy and during follow-up 1 year later. Control biopsies were obtained from nine normal subjects. Muscle capillarity, fiber-type composition and fiber area were analyzed with enzyme- and immunohistochemistry and morphometry. At baseline, CECS patients had lower capillary density (273 vs 378 capillaries/mm(2), P=0.008), lower number of capillaries around muscle fibers (4.5 vs 5.7, P=0.004) and lower number of capillaries in relation to the muscle fiber area (1.1 vs 1.5, P=0.01) compared with normal controls. The fiber-type composition and fiber area did not differ, but focal signs of neuromuscular damage were observed in the CECS samples. At 1-year follow-up after fasciotomy, the fiber area and the number of fibers containing developmental myosin heavy chains were increased, but no enhancement of the capillary network was detected. Thus, morphologically, patients with CECS seemed to have reduced microcirculation capacity. Fasciotomy appeared to trigger a regenerative response in the muscle, however, without any increase in the capillary bed.

  • 6.
    Frykholm, Erik
    et al.
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation.
    Klijn, Peter
    Saey, Didier
    van Hees, Hieronymus W. H.
    Stål, Per
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Sandström, Thomas
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Sörlin, Ann
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation.
    Maltais, François
    Nyberg, Andre
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation.
    Effect and feasibility of non-linear periodized resistance training in people with COPD: study protocol for a randomized controlled trial2019In: Trials, ISSN 1745-6215, E-ISSN 1745-6215, Vol. 20, no 1, article id 6Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: In people with chronic obstructive pulmonary disease (COPD), limb-muscle dysfunction is one of the most troublesome systemic manifestations of the disease, which at the functional level is evidenced by reduced strength and endurance of limb muscles. Improving limb-muscle function is an important therapeutic goal of COPD management, for which resistance training is recommended. However, current guidelines for resistance training in COPD mainly focus on improving muscle strength which only reflects one aspect of limb-muscle function and does not address the issue of reduced muscle endurance. The latter is of importance considering that the reduction in limb-muscle endurance often is greater than that of muscle weakness, and also, limb-muscle endurance seems to be closer related to walking capacity as well as arm function than to limb-muscle strength within this group of people. Thus, strategies targeting multiple aspects of the decreased muscle function are warranted to increase the possibility for an optimal effect for the individual patient. Periodized resistance training, which represents a planned variation of resistance training variables (i.e., volume, intensity, frequency, etc.), is one strategy that could be used to target limb-muscle strength as well as limb-muscle endurance within the same exercise regimen.

    METHODS: This is an international, multicenter, randomized controlled trial comparing the effect and feasibility of non-linear periodized resistance training to traditional non-periodized resistance training in people with COPD. Primary outcomes are dynamic limb-muscle strength and endurance. Secondary outcomes include static limb-muscle strength and endurance, functional performance, quality of life, dyspnea, intramuscular adaptations as well as the proportion of responders. Feasibility of the training programs will be assessed and compared on attendance rate, duration, satisfaction, drop-outs as well as occurrence and severity of any adverse events.

    DISCUSSION: The proposed trial will provide new knowledge to this research area by investigating and comparing the feasibility and effects of non-linear periodized resistance training compared to traditional non-periodized resistance training. If the former strategy produces larger physiological adaptations than non-periodized resistance training, this project may influence the prescription of resistance training in people with COPD.

    TRIAL REGISTRATION: ClinicalTrials.gov, ID: NCT03518723 . Registered on 13 April 2018.

  • 7.
    Granberg, I
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Lindell, Björn
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Eriksson, Per-Olof
    Umeå University, Faculty of Medicine, Department of Odontology, Clinical Oral Physiology.
    Pedrosa-Domellöf, Fatima
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Stål, Per
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Capillary supply in relation to myosin heavy chain fibre composition of human intrinsic tongue muscles2010In: Cells Tissues Organs, ISSN 1422-6405, E-ISSN 1422-6421, Vol. 192, no 5, p. 303-313Article in journal (Refereed)
    Abstract [en]

    The capillary supply and myosin heavy chain (MyHC) composition of three different intrinsic tongue muscles was analysed in the anterior and posterior regions of the human tongue with biochemical and immunohistochemical techniques. Mean capillary density for the whole tongue was 796 ± 82 cap/mm², without regional differences. The overall number of capillaries around each fibre (CAF) was higher in the posterior than in the anterior region (2.5 vs. 2.1, p = 0.009). However, correcting for regional differences in fibre size, CAF per fibre area was higher in the anterior region (4.3 vs. 3.0, p < 0.001). Muscle fibres containing fast MyHCs predominated in the anterior region (78.7%), consisting of MyHCIIa (58.5%), MyHCIIx (1.0%), MyHCIIa+MyHCIIx (11.3%) and MyHCI+MyHCIIa (7.9%). Fibres containing slow MyHC predominated in the posterior region (65.2%), consisting of MyHCI (45.5%) and MyHCI+MyHCIIa (19.7%). A minor fibre population (<2%) contained unusual MyHC isoforms, namely MyHC foetal, MyHC slow-tonic, MyHC α-cardiac or MyHC embryonic. The microvascularization of the human tongue was twice as high as in human limb muscles. Regional similarities in capillary supply, but differences in fibre phenotype composition, suggest that human tongue muscle fibres are fatigue resistant independently of MyHC content. High frequency of hybrid fibres, that is fibres co-expressing two or more MyHC isoforms, indicates a wider spectrum of fibre contractile properties than in limb muscles. In conclusion, human intrinsic tongue muscles showed internal specialization in distribution of MyHC isoforms and capillary supply, but not in the expression of unusual MyHCs.

  • 8.
    Jergović, D
    et al.
    University of Linköping.
    Stål, Per
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Lidman, D
    University of Linköping.
    Lindvall, B
    University of Linköping.
    Hildebrand, C
    University of Linköping.
    Changes in a rat facial muscle after facial nerve injury and repair2001In: Muscle and Nerve, ISSN 0148-639X, E-ISSN 1097-4598, Vol. 24, no 9, p. 1202-1212Article in journal (Refereed)
    Abstract [en]

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

  • 9.
    Johansson, Bengt
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine. Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Mörner, Stellan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Waldenström, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Stål, Per
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Myocardial capillary supply is limited in hypertrophic cardiomyopathy: a morphological analysis2008In: International Journal of Cardiology, ISSN 0167-5273, E-ISSN 1874-1754, Vol. 126, no 2, p. 252-257Article in journal (Refereed)
    Abstract [en]

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

  • 10.
    Kjellgren, Daniel
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Stål, Per
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Larsson, Lars
    Uppsala University.
    Fürst, Dieter
    University of Bonn.
    Pedrosa-Domellöf, Fatima
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy. Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Uncoordinated expression of myosin heavy chains and myosin-binding protein C isoforms in human extraocular muscles2006In: Investigative Ophthalmology and Visual Science, ISSN 0146-0404, E-ISSN 1552-5783, Vol. 47, no 10, p. 4188-4193Article in journal (Refereed)
    Abstract [en]

    PURPOSE: To examine the distribution of myosin-binding protein C (MyBP-C) in human extraocular muscles (EOMs) and to correlate the myosin heavy chain (MyHC) and the MyBP-C composition of the fibers. METHODS: Samples from 17 EOMs, 3 levator palpebrae (LP), and 6 limb muscles were analyzed with SDS-PAGE and immunoblot or processed for immunocytochemistry with monoclonal antibodies (mAbs) against MyBP-C-fast, MyBP-C-slow, MyHCIIa, MyHCI, MyHCsto, MyHCalpha-cardiac, and MyHCemb. RESULTS: In the limb muscle samples, fast fibers were labeled with anti-MyBP-C-fast and anti-MyBP-C-slow, whereas the slow fibers were immunostained with anti-MyBP-C-slow only, in accordance with previous studies. In 11 EOM samples MyBP-C-fast was not detected, and weak staining with anti-MyBP-C-fast was seen only in a few fibers in the proximal part of 2 muscles. The mAb against MyBP-C-slow labeled all fibers, but fibers containing MyHCI were generally more strongly stained. In the levator palpebrae, immunostaining with anti-MyBP-C-fast was present in some fibers labeled with anti-MyHCIIa and/or anti-MyHCeom. MyBP-C-fast and -intermediate were not detected biochemically in the EOMs. CONCLUSIONS: The lack of MyBP-C-fast and intermediate is an additional feature of the human EOM allotype. The true EOMs have a unique myofibrillar protein isoform composition reflecting their special structural and functional properties. The levator palpebrae muscle phenotype is intermediate between that of the EOMs and the limb muscles.

  • 11.
    Lindman, Rolf
    et al.
    University Hospital, Malmö.
    Paulin, Gunnar
    University Hospital, Linköping.
    Stål, Per S
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Morphological characterization of the levator veli palatini muscle in children born with cleft palates2001In: The Cleft Palate-Craniofacial Journal, ISSN 1055-6656, E-ISSN 1545-1569, Vol. 38, no 5, p. 438-448Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: The aim of this study was to analyze, morphologically and biochemically, one of the soft palate muscles, the levator veli palatini (LVP), in children born with cleft palate.

    SUBJECTS AND METHODS: Biopsies were obtained from nine male and three female infants in connection with the early surgical repair of the hard and soft palate. Samples from five adult normal LVP muscles were used for comparison. The muscle morphology, fiber type and myosin heavy chain (MyHC) compositions, capillary supply, and content of muscle spindles were analyzed with different enzyme-histochemical, immunohistochemical, and biochemical techniques.

    RESULTS: Compared with the normal adult subjects, the LVP muscle from the infantile subjects with cleft had a smaller mean fiber diameter, a larger variability in fiber size and form, a higher proportion of type II fibers, a higher amount of fast MyHCs, and a lower density of capillaries. No muscle spindles were observed. Moreover, one-third of the biopsies from the infantile subjects with cleft LVP either lacked muscle tissue or contained only a small amount.

    CONCLUSIONS: The LVP muscle from children with cleft palate has a different morphology, compared with the normal adult muscle. The differences might be related to different stages in maturation of the muscles, changes in functional demands with growth and age, or a consequence of the cleft. The lack of contractile tissue in some of the cleft biopsies offers one possible explanation to a persistent postsurgical velopharyngeal insufficiency in some patients, despite a successful surgical repair.

  • 12.
    Lindman, Rolf
    et al.
    Malmö University Hospital.
    Stål, Per S
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Abnormal palatopharyngeal muscle morphology in sleep-disordered breathing2002In: Journal of the Neurological Sciences, ISSN 0022-510X, E-ISSN 1878-5883, Vol. 195, no 1, p. 11-23, Article Number: PII S0022-510X(01)00676-1Article in journal (Refereed)
    Abstract [en]

    The aim of the present study was to investigate whether histopathological changes can be detected in two soft palate muscles, the palatopharyngeus and the uvula, in 11 patients with long duration of sleep-disordered breathing (SDB). Muscle samples were collected from patients undergoing uvulo-palatopharyngoplasty (UPPP). Reference samples from the corresponding areas were obtained at autopsy from five previously healthy subjects. Muscle morphology, fibre type and myosin heavy chain (MyHC) compositions were analysed with enzyme-histochemical, immunohistochemical and biochemical techniques. The muscle samples from the patients, and especially those from the palatopharyngeus, showed several morphological abnormalities. The most striking findings were (i) increased amount of connective tissue, (ii) abnormal variability in fibre size, (iii) increased proportion of small-sized fibres, (iv) alterations in fibre type and MyHC compositions, (v) increased frequency of fibres containing developmental MyHC isoforms. Our findings point towards a pathological process of denervation and degeneration in the patient samples. Conclusively, the morphological abnormalities suggest a neuromuscular disorder of the soft palate in SDB patients.

  • 13. Nielsen, Rasmus Oestergaard
    et al.
    Schjerling, Peter
    Tesch, Per
    Stål, Per
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Langberg, Henning
    Collagen content in the vastus lateralis and the soleus muscle following a 90-day bed rest period with or without resistance exercises2015In: MLTJ - Muscles Ligaments and Tendons Journal, ISSN 2240-4554, Vol. 5, no 4, p. 305-309Article in journal (Refereed)
    Abstract [en]

    Introduction: spaceflight seems associated with deterioration of the function of the skeletal muscles. Since muscle collagen is critical for muscle function, an improved understanding of the content of the muscle collagen during long-term inactivity seems important. Bed-rest with in-bed resistance training serves as a proxy for the conditions in space. Therefore, ground-based studies may improve the understanding of the consequences of long-term inactivity.

    Purpose: the purpose is to compare the change in collagen protein in the vastus lateralis (VL) and the soleus (SOL) muscle amongst persons exposed to a 90-day bed rest with or without resistance exercise.

    Methods: an explorative analysis was completed based on data from a randomized, controlled trial.The intervention group (BRE, SOL n=4, VL n=8) performed supine-based squat exercises, whereas the controls (BE, SOL n=6, VL n=12) remained inactive during follow-up. Muscle biopsies from vastus lateralis and soleus were taken at baseline(pre) and after 90-days’ follow-up (post). Muscle collagen (μg collagen/mg protein) was quantified. Two-way repeated measurements ANOVA was used to compare the interaction between the intervention (BRE/BR) and time (pre/post) for each muscle.

    Results: the collagen content of VL was similar between pre and post in the BRE group (-3.8 μg collagen/mg protein [95% CI: -22.0; 14.4], p=0.68) while it rose amongst individuals in the BR group (14.9 μg collagen/mg protein [95% CI: -0.01; 29.7], p=0.05). The difference of 18.66 [95% CI: -6.5; 43.9] between BRE and BR across time was, however, not significant (p=0.14). No significant reduction in SOL muscle collagen content was observed from pre to post in the BR group (-9.3 μg collagen/mg protein [95% CI: -24.9; 6.4], p=0.25) or in the BRE group (-6.5 μg collagen/mg protein [95% CI: -25.6; 12.6], p=0.50). There was no difference in the effect of BR versus BRE over time (mean difference -2.78 μg collagen/mg protein[95% CI: -29.7; 24.1], p=0.82).

    Conclusion: muscle collagen content in the VL or SOL muscle does not seem to differ after a 90-day bed rest period with or without squat exercises.

  • 14.
    Pontén, Eva M
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Stål, Per S
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Decreased capillarization and a shift to fast myosin heavy chain IIx in the biceps brachii muscle from young adults with spastic paresis.2007In: J Neurol Sci, ISSN 0022-510X, Vol. 253, no 1-2, p. 25-33Article in journal (Other academic)
    Abstract [en]

    Muscle spasticity and paresis are conditions that occur secondary to upper motor neuron lesions. The co-existence of decreased motor unit recruitment and intermittent over-activity generates confusion concerning the effect on muscle fiber characteristics. In order to increase the knowledge about the effect of upper motor lesion on capillarization and muscle fiber composition, the biceps brachii muscle from seven young adults with long duration of spastic paresis and seven age-matched controls were analyzed using morphological and enzyme- and immuno-histochemical techniques. The spastic muscles had a 38% lower capillary density (p=0.002), 30% fewer capillaries around each muscle fiber (p=0.02), and 16% fewer capillaries when related to the fiber size (p=0.04). The frequency of fibers expressing myosin heavy chain (MyHC) IIx increased (30% vs. 4%, p=0.006), while the percentage of fibers expressing MyHC I and MyHC IIa, respectively, decreased (22% vs. 46% and 7% vs. 29%, p&lt;0.01). The high proportion of muscle fibers with low oxidative capacity and low capillary supply indicates that biceps brachii muscle from patients with upper motor lesions fatigue more easily than normal controls. We also observed a significantly higher variability in fiber size for fibers expressing MyHC I (p&lt;0.04), and, in three of the subjects, a small amount of small fibers expressing developmental MyHCs was found. These results suggest that, although intermittent stretch reflex contractions might have an impact on the muscle characteristics in spastic paresis, the muscle phenotypic properties are more adapted to decreased voluntary motor unit recruitment.

  • 15.
    Pontén, Eva
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Stål, Per
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Capillarization and myosin composition in spastic biceps brachii muscleManuscript (preprint) (Other academic)
  • 16.
    Renström, Lina
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Song, Yafeng
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Stål, Per
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Forsgren, Sture
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    TNF-alpha in an Overuse Muscle Model - Relationship to Muscle Fiber Necrosis/Regeneration, the NK-1 Receptor and an Occurrence of Bilateral Involvement2013In: Journal Clinical & Cellular Immunology, ISSN 2155-9899, Vol. 4, no 2Article in journal (Refereed)
    Abstract [en]

    TNF-alphais known to be involved in muscle damage and inflammation (myositis). Therelationships between the TNF-alpha system and muscle fibernecrosis/regeneration and the tachykinin system in this situation are unclear.We have an experimental rabbit model related to unilateral muscle overuse whichleads to marked muscle derangement and myositis bilaterally. Using this model,staining for TNF-alpha, in parallel with staining for the substance P-preferredreceptor (NK-1R) and desmin were performed. Desmin staining was used as areference concerning identification of degeneration/regeneration and the soleusmuscle was the muscle examined. It was observed that the inflammatory cells, aswell as blood vessel walls in the myositis areas, expressed TNF-alpha mRNA.Muscle fibers that were interpreted to represent necrotic fibers expressedTNF-alpha mRNA reactions and showed NK-1R immunoreactions, the reactions beingconfined to white blood cells that had infiltrated into the fibers. Musclefibers that were interpreted to be in a regenerative state expressedpatchy/widespread TNF-alpha mRNA and point like NK-1R immunoreactions. Abnormalmuscle fibers thus showed TNF-alpha mRNA as well as NK-1R immunoreactions.Normal muscle fibers never showed these reactions. Occurrence of inflammatorycell and muscle fiber TNF-alpha mRNA reactions was equally marked in the myositisareas of the contralateral side as in these areas of the ipsilateralexperimental side. The observations show that the TNF-alpha system is muchinvolved in the processes that occur in the muscle derangement/myositisprocesses. The involvement relates to effects in processes of both regenerationand muscle fiber necrosis. It may be that substance P via activation throughthe NK-1R influences the TNF-alpha expression. The findings of TNF-alphaupregulation also for the contralateral side show that the TNF-alpha system isinvolved both ipsi and contralaterally during the development of myosits/muscleaffection in response to unilateral overuse.

  • 17.
    Renström, Lina
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Stål, Per
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Song, Yafeng
    Forsgren, Sture
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Bilateral muscle fiber and nerve influences by TNF-alpha in response to unilateral muscle overuse: studies on TNF receptor expressions2017In: BMC Musculoskeletal Disorders, ISSN 1471-2474, E-ISSN 1471-2474, Vol. 18, no 1, article id 498Article in journal (Other academic)
    Abstract [en]

    Background:

    TNF-alpha is suggested to be involved in muscle damage and muscle inflammation (myositis). In order to evaluate whether TNF-alpha is involved in the myositis that occurs in response to muscle overuse, the aim was to examine the expression patterns of TNF receptors in this condition.

    Methods:

    A rabbit muscle overuse model leading to myositis in the soleus muscle was used. The expression patterns of the two TNF receptors Tumor Necrosis Factor Receptor type 1 (TNFR1) and Tumor Necrosis Factor Receptor type 2 (TNFR2) were investigated. In situ hybridization and immunofluorescence were utilized. Immunostainings for desmin, NK-1R and CD31 were made in parallel.

    Results:

    Immunoreactions (IR) for TNF receptors were clearly observed in white blood cells, fibroblasts and vessel walls, and most interestingly also in muscle fibers and nerve fascicles in the myositis muscles. There were very restricted reactions for these in the muscles of controls. The upregulation of TNF receptors was for all types of structures seen for both the experimental side and the contralateral nonexperimental side. TNF receptor expressing muscle fibers were present in myositis muscles. They can be related to attempts for reparation/regeneration, as evidenced from results of parallel stainings. Necrotic muscle fibers displayed TNFR1 mRNA and TNFR2 immunoreaction (IR) in the invading white blood cells. In myositis muscles, TNFR1 IR was observed in both axons and Schwann cells while TNFR2 IR was observed in Schwann cells. Such observations were very rarely made for control animals.

    Conclusions:

    The findings suggest that there is a pronounced involvement of TNF-alpha in the developing myositis process. Attempts for reparation of the muscle tissue seem to occur via both TNFR1 and TNFR2. As the myositis process also occurs in the nonexperimental side and as TNF receptors are confined to nerve fascicles bilaterally it can be asked whether TNF-alpha is involved in the spreading of the myositis process to the contralateral side via the nervous system. Taken together, the study shows that TNF-alpha is not only associated with the inflammation process but that both the muscular and nervous systems are affected and that this occurs both on experimental and nonexperimental sides.

  • 18.
    Shah, Farhan
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Berggren, Diana
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    Holmlund, Thorbjörn
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    Levring Jäghagen, Eva
    Umeå University, Faculty of Medicine, Department of Odontology.
    Stål, Per
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Unique expression of cytoskeletal proteins in human soft palate muscles2016In: Journal of Anatomy, ISSN 0021-8782, E-ISSN 1469-7580, Vol. 228, no 3, p. 487-494Article in journal (Refereed)
    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.

  • 19.
    Shah, Farhan
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Forsgren, Sture
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Holmlund, Thorbjörn
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    Jaghagen, Eva Levring
    Umeå University, Faculty of Medicine, Department of Odontology.
    Berggren, Diana
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    Franklin, Karl A.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences.
    Stål, Per
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Neurotrophic factor BDNF is upregulated in soft palate muscles of snorers and sleep apnea patients2019In: Laryngoscope Investigative Otolaryngology, ISSN 2378-8038, Vol. 4, no 1, p. 174-180Article in journal (Refereed)
    Abstract [en]

    Objectives: Neuromuscular injuries are suggested to contribute to upper airway collapse and swallowing dysfunction in patients with sleep apnea. Neurotrophins, a family of proteins involved in survival, development, and function of neurons, are reported to be upregulated in limb muscle fibers in response to overload and nerve damage. We aimed to investigate the expression of two important neurotrophins, brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF), in muscle fibers of uvula from snorers and sleep apnea patients and to compare these findings with pharyngeal function.

    Methods: Uvula muscle biopsies from 22 patients and 10 controls were analyzed for BDNF, NGF, and cytoskeletal protein desmin using immunohistochemistry. Pharyngeal swallowing function was assessed using videoradiography.

    Results: BDNF, but not NGF, was significantly upregulated in a subpopulation of muscle fibers in snoring and sleep apnea patients. Two major immunoreaction patterns for BDNF were observed; a fine grainy point like BDNF staining was displayed in muscle fibers of both patients and controls (41 +/- 23 vs. 25 +/- 17%, respectively, P = .06), while an abnormal upregulated intense-dotted or disorganized reaction was mainly observed in patients (8 +/- 8 vs. 2 +/- 2%, P = .02). The latter fibers, which often displayed an abnormal immunoreaction for desmin, were more frequent in patients with than without swallowing dysfunction (10 +/- 8 vs. 3 +/- 3%, P = .05).

    Conclusion: BDNF is upregulated in the upper airway muscles of snorers and sleep apnea patients, and especially in patients with swallowing dysfunction. Upregulation of BDNF is suggested to be a response to denervation, reinnervation, and repair of injured muscle fibers. Our findings propose that damaged upper airway muscles might heal following treatment for snoring and sleep apnea.

  • 20.
    Shah, Farhan
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). Laboratory of Muscle Biology, IMB, Umeå University.
    Forsgren, Sture
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Holmlund, Thorbjörn
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    Levring Jäghagen, Eva
    Umeå University, Faculty of Medicine, Department of Odontology.
    Berggren, Diana
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    Franklin, Karl A.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences.
    Stål, Per
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Upregulated expression of brain-derived neurotrophic factor in soft palate muscles of snorers and obstructive sleep apnea patientsManuscript (preprint) (Other academic)
  • 21.
    Shah, Farhan
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Franklin, Karl A
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Holmlund, Thorbjörn
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    Levring Jäghagen, Eva
    Umeå University, Faculty of Medicine, Department of Odontology.
    Berggren, Diana
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    Forsgren, Sture
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Stål, Per
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Desmin and dystrophin abnormalities in upper airway muscles of snorers and patients with sleep apnea2019In: Respiratory Research, ISSN 1465-993X, Vol. 20, article id 31Article in journal (Refereed)
    Abstract [en]

    The pathophysiology of obstruction and swallowing dysfunction in snores and sleep apnea patients remains unclear. Neuropathy and to some extent myopathy have been suggested as contributing causes. Recently we reported an absence and an abnormal isoform of two cytoskeletal proteins, desmin, and dystrophin, in upper airway muscles of healthy humans. These cytoskeletal proteins are considered vital for muscle function. We aimed to investigate for muscle cytoskeletal abnormalities in upper airways and its association with swallowing dysfunction and severity of sleep apnea. Cytoskeletal proteins desmin and dystrophin were morphologically evaluated in the uvula muscle of 22 patients undergoing soft palate surgery due to snoring and sleep apnea and in 10 healthy controls. The muscles were analysed with immunohistochemical methods, and swallowing function was assessed using videoradiography. Desmin displayed a disorganized pattern in 21 +/- 13% of the muscle fibres in patients, while these fibers were not present in controls. Muscle fibres lacking desmin were present in both patients and controls, but the proportion was higher in patients (25 +/- 12% vs. 14 +/- 7%, p = 0.009). The overall desmin abnormalities were significantly more frequent in patients than in controls (46 +/- 18% vs. 14 +/- 7%, p < 0.001). In patients, the C-terminus of the dystrophin molecule was absent in 19 +/- 18% of the desmin-abnormal muscle fibres. Patients with swallowing dysfunction had 55 +/- 10% desmin-abnormal muscle fibres vs. 22 +/- 6% in patients without swallowing dysfunction, p = 0.002. Cytoskeletal abnormalities in soft palate muscles most likely contribute to pharyngeal dysfunction in snorers and sleep apnea patients. Plausible causes for the presence of these abnormalities is traumatic snoring vibrations, tissue stretch or muscle overload.

  • 22.
    Shah, Farhan
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). Laboratory of Muscle Biology, IMB, Umeå University.
    Franklin, Karl
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences.
    Holmlund, Thorbjörn
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    Levring Jäghagen, Eva
    Umeå University, Faculty of Medicine, Department of Odontology.
    Berggren, Diana
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    Forsgren, Sture
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Stål, Per
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Desmin and dystrophin myopathy in the upper airway of snoring and obstructive sleep apnea patientsManuscript (preprint) (Other academic)
  • 23.
    Shah, Farhan
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Holmlund, Thorbjörn
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    Levring Jäghagen, Eva
    Umeå University, Faculty of Medicine, Department of Odontology.
    Berggren, Diana
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    Franklin, Karl A
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Forsgren, Sture
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Stål, Per
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Axon and Schwann Cell Degeneration in Nerves of Upper Airway Relates to Pharyngeal Dysfunction in Snorers and Patients With Sleep Apnea2018In: Chest, ISSN 0012-3692, E-ISSN 1931-3543, Vol. 154, no 5, p. 1091-1098Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The pathophysiologic mechanism of nocturnal obstruction and swallowing dysfunction commonly occurring in patients with sleep apnea is unclear. The goal of this study was to investigate whether nerve injuries in the upper airways of snorers and patients with sleep apnea are associated with pharyngeal dysfunction and severity of sleep apnea.

    METHODS: Twenty-two patients undergoing palatal surgery due to snoring and sleep apnea were investigated for a swallowing dysfunction by using videoradiography. Twelve healthy nonsnoring subjects were included as control subjects. Tissue samples from the soft palate at the base of the uvula were obtained in all patients and control subjects. Nerves and muscle were analyzed with immunohistochemical and morphologic methods, and the findings were correlated with swallowing function and degree of sleep apnea.

    RESULTS: In the soft palate of patients, nerve fascicles exhibited a significantly lower density of axons (5.4 vs 17.9 x 10(-3) axons/mu m(2); P = .02), a smaller percentage area occupied by Schwann cells (17.5% vs 45.2%; P = .001) and a larger number of circular shaped Schwann cells lacking central axons (43.0% vs 12.7%; P < 0.001) compared with control subjects. The low density of axons was significantly related to degree of swallowing dysfunction (r = 0.5; P = .03) and apnea-hypopnea index > 5 (P = .03). Regenerating axons were frequently observed in patients compared with control subjects (11.3 +/- 4.2% vs 4.8 +/- 2.4%; P = .02).

    CONCLUSIONS: Axon degeneration in preterminal nerves of the soft palate is associated with pharyngeal dysfunction in snorers and patients with sleep apnea. The most likely cause for the nerve injuries is traumatic snoring vibrations and tissue stretch, leading to swallowing dysfunction and increased risk for upper airway obstruction during sleep.

  • 24.
    Shah, Farhan
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). Laboratory of Muscle Biology, IMB, Umeå University.
    Holmlund, Thorbjörn
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    Levring Jäghagen, Eva
    Umeå University, Faculty of Medicine, Department of Odontology.
    Berggren, Diana
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    Franklin, Karl A.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences.
    Forsgren, Sture
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Stål, Per
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Axon and Schwann cell degeneration in nerves of upper airway relates to pharyngeal dysfunction in snorers and sleep apnea patientsManuscript (preprint) (Other academic)
  • 25.
    Shah, Farhan
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). Prosthodontics, Faculty of Dentistry, University of Toronto, Ontario, Canada.
    Stål, Per
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Li, Jian
    Sessle, Barry J.
    Avivi-Arber, Limor
    Tooth extraction and subsequent dental implant placement in Sprague-Dawley rats induce differential changes in anterior digastric myofibre size and myosin heavy chain isoform expression2019In: Archives of Oral Biology, ISSN 0003-9969, E-ISSN 1879-1506, Vol. 99, p. 141-149Article in journal (Refereed)
    Abstract [en]

    Objective: to determine if tooth loss and dental implant placement in rats induce changes in the morphological and histochemical features of the Anterior Digastric muscle.

    Design: Adult male Sprague-Dawley rats had their right maxillary molar teeth extracted. ‘Extraction-1’ and ‘Extraction-2 groups were sacrificed, respectively, 4 or 8 weeks later, and an Implant group had an implant placement 2 weeks after the molar extraction, and rats were sacrificed 3 weeks later (n = 4/group). Naive rats (n = 3) had no treatment. Morphometric and immunohistochemical techniques quantified Anterior Digastric muscle myofibres’ cross-sectional area (CSA) and myosin heavy chain (MyHC) isoform proportions. Significant ANOVAs were followed by post-hoc tests; p < 0.05 and 0.1 were considered to reflect levels of statistical significance.

    Results: In naïve rats, the peripheral regions of the Anterior Digastric muscle was dominated by MyHC-IIx/b isoform and there were no MyHC-I isoforms; the central regions dominated by MyHC-IIx/b and MyHC-IIa isoforms. Compared with naive rats, tooth extraction produced, 8 (but not 4) weeks later, a decreased proportion of fast-contracting fatigue-resistant MyHC-IIa isoform (p = 0.08), and increased proportion of fast and intermediate fatigue-resistance MyHC-IIa/x/b isoform (p = 0.03). Dental implant placement following tooth extraction attenuated the extraction effects but produced a decreased proportion of fast-contracting fatiguable MyHC-llx/b isoform (p = 0.03) in the peripheral region, and increased inter-animal variability in myofibre-CSAs.

    Conclusions: Given the crucial role that the Anterior Digastric muscle plays in many vital oral functions (e.g., chewing, swallowing), these changes may contribute to the changes in oral sensorimotor functions that occur in humans following such treatments.

  • 26.
    Song, Yafeng
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Forsgren, Sture
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Liu, Jing Xia
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Yu, Jiguo
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Sports Medicine.
    Stål, Per
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Unilateral muscle overuse causes bilateral changes in muscle fibre composition and vascular supplyManuscript (preprint) (Other academic)
  • 27.
    Song, Yafeng
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Forsgren, Sture
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Liu, Jing-Xia
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Yu, Ji-Guo
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Sports Medicine.
    Stål, Per
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Unilateral muscle overuse causes bilateral changes in muscle fiber composition and vascular supply2014In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 9, no 12, p. e116455-Article in journal (Refereed)
    Abstract [en]

    Unilateral strength training can cause cross-transfer strength effects to the homologous contralateral muscles. However, the impact of the cross-over effects on the muscle tissue is unclear. To test the hypothesis that unilateral muscle overuse causes bilateral alterations in muscle fiber composition and vascular supply, we have used an experimental rabbit model with unilateral unloaded overstrain exercise via electrical muscle stimulation (E/EMS). The soleus (SOL) and gastrocnemius (GA) muscles of both exercised (E) and contralateral non-exercised (NE) legs (n = 24) were morphologically analyzed after 1w, 3w and 6w of EMS. Non-exercised rabbits served as controls (n = 6). After unilateral intervention the muscles of both E and NE legs showed myositis and structural and molecular tissue changes that to various degrees mirrored each other. The fiber area was bilaterally smaller than in controls after 3w of E/EMS in both SOL (E 4420 and NE 4333 µm2 vs. 5183 µm2, p<0.05) and GA (E 3572 and NE 2983 µm2 vs. 4697 µm2, p<0.02) muscles. After 6w of E/EMS, the percentage of slow MyHCI fibers was lower than in controls in the NE legs of SOL (88.1% vs. 98.1%, p<0.009), while the percentage of fast MyHCIIa fibers was higher in the NE legs of GA (25.7% vs. 15.8%, p = 0.02). The number of capillaries around fibers in the E and NE legs was lower (SOL 13% and 15%, respectively, GA 25% and 23%, respectively, p<0.05) than in controls. The overall alterations were more marked in the fast GA muscle than in the slow SOL muscle, which on the other hand showed more histopathological muscle changes. We conclude that unilateral repetitive unloaded overuse exercise via EMS causes myositis and muscle changes in fiber type proportions, fiber area and fiber capillarization not only in the exercised leg, but also in the homologous muscles in the non-exercised leg.

  • 28.
    Song, Yafeng
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Forsgren, Sture
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Yu, Jiguo
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Sports Medicine.
    Lorentzon, Ronny
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Sports Medicine.
    Stål, Per
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Effects on contralateral muscles after unilateral electrical muscle stimulation and exercise2012In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 7, no 12, p. e52230-Article in journal (Refereed)
    Abstract [en]

    It is well established that unilateral exercise can produce contralateral effects. However, it is unclear whether unilateral exercise that leads to muscle injury and inflammation also affects the homologous contralateral muscles. To test the hypothesis that unilateral muscle injury causes contralateral muscle changes, an experimental rabbit model with unilateral muscle overuse caused by a combination of electrical muscle stimulation and exercise (EMS/E) was used. The soleus and gastrocnemius muscles of both exercised and non-exercised legs were analyzed with enzyme-and immunohistochemical methods after 1, 3 and 6 weeks of repeated EMS/E. After 1 w of unilateral EMS/E there were structural muscle changes such as increased variability in fiber size, fiber splitting, internal myonuclei, necrotic fibers, expression of developmental MyHCs, fibrosis and inflammation in the exercised soleus muscle. Only limited changes were found in the exercised gastrocnemius muscle and in both non-exercised contralateral muscles. After 3 w of EMS/E, muscle fiber changes, presence of developmental MyHCs, inflammation, fibrosis and affections of nerve axons and AChE production were observed bilaterally in both the soleus and gastrocnemius muscles. At 6 w of EMS/E, the severity of these changes significantly increased in the soleus muscles and infiltration of fat was observed bilaterally in both the soleus and the gastrocnemius muscles. The affections of the muscles were in all three experimental groups restricted to focal regions of the muscle samples. We conclude that repetitive unilateral muscle overuse caused by EMS/E overtime leads to both degenerative and regenerative tissue changes and myositis not only in the exercised muscles, but also in the homologous non-exercised muscles of the contralateral leg. Although the mechanism behind the contralateral changes is unclear, we suggest that the nervous system is involved in the cross-transfer effects.

  • 29.
    Song, Yafeng
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Stål, Per
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Lorentzon, Ronny
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Sports Medicine.
    Backman, C
    Yu, Jiguo
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Sports Medicine.
    Forsgren, Sture
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Experimental studies favour that tachykinins are involved in the process of myositis and muscle derangement in an overuse animal modelManuscript (preprint) (Other academic)
  • 30.
    Song, Yafeng
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Stål, Per S
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Yu, Ji-Guo
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Sports Medicine.
    Lorentzon, Ronny
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Sports Medicine.
    Backman, Clas
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Hand Surgery.
    Forsgren, Sture
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Inhibitors of endopeptidase and angiotensin-converting enzyme lead to an amplification of the morphological changes and an upregulation of the substance P system in a muscle overuse model2014In: BMC Musculoskeletal Disorders, ISSN 1471-2474, E-ISSN 1471-2474, Vol. 15, p. 126-Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: We have previously observed, in studies on an experimental overuse model, that the tachykinin system may be involved in the processes of muscle inflammation (myositis) and other muscle tissue alterations. To further evaluate the significance of tachykinins in these processes, we have used inhibitors of neutral endopeptidase (NEP) and angiotensin-converting enzyme (ACE), substances which are known to terminate the activity of various endogenously produced substances, including tachykinins.

    METHODS: Injections of inhibitors of NEP and ACE, as well as the tachykinin substance P (SP), were given locally outside the tendon of the triceps surae muscle of rabbits subjected to marked overuse of this muscle. A control group was given NaCl injections. Evaluations were made at 1 week, a timepoint of overuse when only mild inflammation and limited changes in the muscle structure are noted in animals not treated with inhibitors. Both the soleus and gastrocnemius muscles were examined morphologically and with immunohistochemistry and enzyme immunoassay (EIA).

    RESULTS: A pronounced inflammation (myositis) and changes in the muscle fiber morphology, including muscle fiber necrosis, occurred in the overused muscles of animals given NEP and ACE inhibitors. The morphological changes were clearly more prominent than for animals subjected to overuse and NaCl injections (NaCl group). A marked SP-like expression, as well as a marked expression of the neurokinin-1 receptor (NK-1R) was found in the affected muscle tissue in response to injections of NEP and ACE inhibitors. The concentration of SP in the muscles was also higher than that for the NaCl group.

    CONCLUSIONS: The observations show that the local injections of NEP and ACE inhibitors led to marked SP-like and NK-1R immunoreactions, increased SP concentrations, and an amplification of the morphological changes in the tissue. The injections of the inhibitors thus led to a more marked myositis process and an upregulation of the SP system. Endogenously produced substances, out of which the tachykinins conform to one substance family, may play a role in mediating effects in the tissue in a muscle that is subjected to pronounced overuse.

  • 31.
    Song, Yafeng
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Stål, Per
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Yu, Jiguo
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Sports Medicine.
    Forsgren, Sture
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Bilateral increase in expression and concentration of tachykinin in a unilateral rabbit muscle overuse model that leads to myositis2013In: BMC Musculoskeletal Disorders, ISSN 1471-2474, E-ISSN 1471-2474, Vol. 14, article id 134Article in journal (Refereed)
    Abstract [en]

    Background: Tachykinins can have pro-inflammatory as well as healing effects during tissue reorganization and inflammation. Recent studies report an up-regulation in the expression of the substance P (SP)-preferred receptor, the neurokinin-1 receptor, in marked muscle inflammation (myositis). There is, however, only very little information on the expression patterns and levels of tachykinins in this situation.

    Methods: The tachykinin system was analyzed using a rabbit experimental model of muscle overuse, whereby unilateral muscle exercise in combination with electrical stimulation led to muscle derangement and myositis in the triceps surae muscle (experimental length 1--6 weeks). Evaluations were made for both parts of the muscle (soleus and gastrocnemius muscles) in experimental and non-experimental (contralateral) sides. Morphologic evaluation, immunohistochemistry, in situ hybridization and enzyme immunoassay (EIA) analyses were applied.

    Results: Myositis and muscle derangement occurred focally not only in the experimental side but also in the non-experimental side. In the inflammatory areas (focal myositis areas), there were frequent nerve fibers showing tachykinin-like immunoreactivity and which were parts of nerve fascicles and which were freely dispersed in the tissue. Cells in the inflammatory infiltrates showed tachykinin-like immunoreactivity and tachykinin mRNA expression. Specific immunoreactivity and mRNA expression were noted in blood vessel walls of both sides, especially in focally affected areas. With increasing experimental length, we observed an increase in the degree of immunoreactivity in the vessel walls. The EIA analyses showed that the concentration of tachykinin in the tissue on both sides increased in a time-dependent manner. There was a statistical correlation in the concentration of tachykinin and the level of tachykinin immunoreactivity in the blood vessel walls between experimental and non-experimental sides.

    Conclusions: The observations show an up-regulation of the tachykinin system bilaterally during muscle derangement/myositis in response to pronounced unilateral muscle overuse. This up-regulation occurred in inflammatory areas and was related not only to increased tachykinin innervation but also to tachykinin expression in blood vessel walls and inflammatory cells. Importantly, the tachykinin system appears to be an important factor not only ipsilaterally but also contralaterally in these processes.

  • 32.
    Song, Yafeng
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Stål, Per
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Yu, Jiguo
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Sports Medicine.
    Forsgren, Sture
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Marked effects of tachykinin in myositis both in the experimental side and contralaterally: studies on NK-1 receptor expressions in an animal model2013In: ISRN Inflammation, ISSN 2090-8695, Vol. 2013, no 907821Article in journal (Refereed)
    Abstract [en]

    Muscle injury and inflammation (myositis) in a rabbit model of an unilateral muscle overuse were examined. It is unknown if the tachykinin system has a functional role in this situation. In this study, therefore, the neurokinin-1 receptor (NK-1R) expression patterns were evaluated. White blood cells, nerve fascicles, fine nerve fibers, and blood vessel walls in myositis areas showed NK-1R immunoreaction. NK-1R mRNA reactions were observable for white blood cells and blood vessel walls of these areas. NK-1R immunoreaction and NK-1R mRNA reactions were also seen for muscle fibers showing degenerative and regenerative features. There were almost no NK-1R immunoreactions in normal muscle tissue. Interestingly, marked NK-1R expressions were seen for myositis areas of both the experimental side and the contralateral nonexperimental side. EIA analyses showed that the concentration of substance P in the muscle tissue was clearly increased bilaterally at the experimental end stage, as compared to the situation for normal muscle tissue. These observations show that the tachykinin system is very much involved in the processes that occur in muscle injury/myositis. The effects can be related to proinflammatory effects and/or tissue repair. The fact that there are also marked NK-1R expressions contralaterally indicate that the tachykinin system has crossover effects.

  • 33.
    Stål, Per
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Lindman, R
    Clinic of Orthodontics and Postgraduate Education and Department of Orthodontics, Malmö University, Malmö.
    Characterisation of human soft palate muscles with respect to fibre types, myosins and capillary supply.2000In: Journal of Anatomy, ISSN 0021-8782, E-ISSN 1469-7580, Vol. 197 ( Pt 2), p. 275-90Article in journal (Refereed)
    Abstract [en]

    Four human soft palate muscles, and palatopharyngeus, the uvula, the levator and tensor veli palatini were examined using enzyme-histochemical, immunohistochemical and biochemical methods and compared with human limb and facial muscles. Our results showed that each palate muscle had a distinct morphological identity and that they generally shared more similarities with facial than limb muscles. The palatopharyngeus and uvula muscles contained 2 of the highest proportions of type II fibres ever reported for human muscles. In contrast, the levator and tensor veli palatini muscles contained predominantly type I fibres. A fetal myosin heavy chain isoform (MyHC), not usually found in normal adult limb muscles, was present in a small number of fibres in all palate muscles. The mean muscle fibre diameter was smaller than in limb muscles and the individual and intramuscular variability in diameter and shape was considerable. All palate muscles had a high capillary density and an unusually high mitochondrial enzyme activity in the type II fibres, in comparison with limb muscles. No ordinary muscle spindles were observed. The fibre type and MyHC composition indicate that the palatopharyngeus and uvula muscles are functionally involved in quick movements whereas the levator and tensor veli palatini muscles perform slower and more continuous contractions. The high aerobic capacity and the rich capillarisation suggest that the palate muscles are relatively fatigue resistant. Absence of ordinary muscle spindles indicates a special proprioceptive control system. The special morphology of the palate muscles may be partly related to the unique anatomy with only one skeletal insertion, a feature consistent with muscle work at low load and tension and which may influence the cytoarchitecture of these muscles. Other important factors determining the special morphological characteristics might be specific functional requirements, distinct embryological origin and phylogenetic factors.

  • 34.
    Stål, Per
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Lindman, Rolf
    Department of Oral and Maxillofacial Surgery and Jaw Orthopedics, Malmö University Hospital, Malmö, Sweden.
    Johansson, Bengt
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine. Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Capillary supply of the soft palate muscles is reduced in long-term habitual snorers2009In: Respiration, ISSN 0025-7931, E-ISSN 1423-0356, Vol. 77, no 3, p. 303-310Article in journal (Refereed)
    Abstract [en]

    Background: Snoring and obstructive sleep apnea (OSA) cause vibration and stretch of the upper airway tissues that may result in neuromuscular damage and changes in the microcirculation. Objectives: The aim of this investigation was to test whether long-term snoring affects capillary supply in soft palate muscles. Methods: Samples from the palatopharyngeus (PP) and uvula (UV) muscles were collected from 8 patients undergoing uvulo-palatopharyngoplasty because of habitual snoring and OSA. Control samples were obtained at autopsy. The muscles were analyzed using immunohistochemistry and morphometry. Results: The patients' palate muscles had a lower capillary density (PP 443 vs. 711 capillaries/mm(2), p < 0.001, and UV 452 vs. 624 capillaries/mm(2), p = 0.009), a lower number of capillaries related to an individual muscle fiber (PP 1.3 vs. 2.7, p = 0.003, and UV 1.0 vs. 1.9, p = 0.03) and a lower number of capillaries related to the fiber size (PP 0.9 vs. 2.1, p = 0.001, and UV 0.6 vs. 1.9, p = 0.002). Conclusions: Our results indicate that reduced capillary supply of palate muscles plays a pathophysiological role in long-term snorers and OSA. The cause of the low capillary supply is unclear, but neuromuscular injury due to repeated vibratory and stretch trauma of the soft palate during snoring is a plausible mechanism.

  • 35.
    Stål, Per
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Marklund, Susanna
    Umeå University, Faculty of Medicine, Department of Odontology, Clinical Oral Physiology.
    Thornell, Lars-Eric
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    De Paul, R
    Eriksson, Per-Olof
    Umeå University, Faculty of Medicine, Department of Odontology, Clinical Oral Physiology.
    Fibre composition of human intrinsic tongue muscles.2003In: Cells Tissues Organs, ISSN 1422-6405, E-ISSN 1422-6421, Vol. 173, no 3, p. 147-161Article in journal (Refereed)
    Abstract [en]

    The muscle fibre composition of three human intrinsic tongue muscles, the longitudinalis, verticalis and transversus, was investigated in four anterior to posterior regions of the tongue using morphological and enzyme- and immunohistochemical techniques. All three muscles typically contained type I, IIA and IM/IIC fibres. Type I fibres expressed slow myosin heavy chain (MyHC), type II fibres fast MyHC, mainly fast A MyHC, whereas type IM/IIC coexpressed slow and fast MyHCs. Type II fibres were in the majority (60%), but regional differences in proportion and diameter of fibre types were obvious. The anterior region of the tongue contained a predominance of relatively small type II fibres (71%), in contrast to the posterior region which instead showed a majority of larger type I and type IM/IIC fibres (66%). In general, the fibre diameter was larger in the posterior region. This muscle fibre composition of the tongue differs from those of limb, orofacial and masticatory muscles, probably reflecting genotypic as well as phenotypic functional specialization in oral function. The predominance of type II fibres and the regional differences in fibre composition, together with intricate muscle structure, suggest generally fast and flexible actions in positioning and shaping the tongue, during vital tasks such as mastication, swallowing, respiration and speech. Copyright 2003 S. Karger AG, Basel

  • 36.
    Stål, Per S
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Johansson, Bengt
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Abnormal Mitochondria Organization and Oxidative Activity in the Palate Muscles of Long-Term Snorers with Obstructive Sleep Apnea2012In: Respiration, ISSN 0025-7931, E-ISSN 1423-0356, Vol. 83, no 5, p. 407-417Article in journal (Refereed)
    Abstract [en]

    Background: Histopathological alterations and a reduced number of capillaries have been observed in the palate muscles of snorers with obstructive sleep apnea syndrome (OSAS). These changes may create a substrate for decreased microcirculation, impaired aerobic metabolism and muscle dysfunction and contribute to upper airway obstruction during sleep. Objectives: The aim was to analyze mitochondria distribution and oxidative enzyme activity in relation to capillary supply in the palate muscles of patients with a history of long-term snoring and OSAS. Methods: Palatopharyngeus (PP) and uvula (UV) muscle samples were obtained from 8 patients undergoing uvulopalatopharyngoplasty due to habitual snoring and OSAS. The muscles were analyzed with enzyme- and immunohistochemistry and morphometry. Results: Abnormalities in the internal organization of mitochondria and oxidative activity were observed in 39 ± 15% of the fibers in the PP and 4 ± 3% in the UV, but not in control samples. The majority of these fibers had a lobulated contour and trabecular internal organization of mitochondria. The number of capillaries around abnormal fibers (PP 0.9 ± 0.3, UV 0.4 ± 0.1) was lower than in fibers of a normal appearance in both patients (PP 1.4 ± 0.6, UV 1.2 ± 0.3) and references (PP 2.7 ± 0.7, UV 1.9 ± 0.9) (p < 0.05). Conclusions: Abnormal mitochondrial distribution, a low capillary supply and signs of impaired oxidative activity suggest that muscle dysfunction of the palate muscles in long-term snorers may contribute to the upper airway obstruction during sleep. The cause of these abnormalities remains unclear, but local muscle and nerve trauma due to vibration and stretch is a possible etiology.

  • 37.
    Thornell, Lars-Eric
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Carlsson, Lena
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Eriksson, Per-Olof
    Umeå University, Faculty of Medicine, Department of Odontology, Clinical Oral Physiology.
    Liu, Jing-Xia
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Österlund, Catharina
    Stål, Per
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Pedrosa-Domellöf, Fatima
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Fibre typing of intrafusal fibres2015In: Journal of Anatomy, ISSN 0021-8782, E-ISSN 1469-7580, Vol. 227, no 2, p. 136-156Article, review/survey (Refereed)
    Abstract [en]

    The first descriptions of muscle spindles with intrafusal fibres containing striated myofibrils and nervous elements were given approximately 150years ago. It took, however, another 100years to establish the presence of two types of intrafusal muscle fibres: nuclear bag and nuclear chain fibres. The present paper highlights primarily the contribution of Robert Banks in fibre typing of intrafusal fibres: the confirmation of the principle of two types of nuclear bag fibres in mammalian spindles and the variation in occurrence of a dense M-band along the fibres. Furthermore, this paper summarizes how studies from the Umea University group (Laboratory of Muscle Biology in the Department of Integrative Medical Biology) on fibre typing and the structure and composition of M-bands have contributed to the current understanding of muscle spindle complexity in adult humans as well as to muscle spindle development and effects of ageing. The variable molecular composition of the intrafusal sarcomeres with respect to myosin heavy chains and M-band proteins gives new perspectives on the role of the intrafusal myofibrils as stretch-activated sensors influencing tension/stiffness and signalling to nuclei.

  • 38.
    Tran, Phong
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Wanrooij, Paulina H.
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Lorenzon, Paolo
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Sharma, Sushma
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Thelander, Lars
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Nilsson, Anna Karin
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Olofsson, Anna-Karin
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Medini, Paolo
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    von Hofsten, Jonas
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). Umeå University, Faculty of Medicine, Umeå Centre for Molecular Medicine (UCMM).
    Stål, Per
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Chabes, Andrei
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics. Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS).
    De novo dNTP production is essential for normal postnatal murine heart development2019In: Journal of Biological Chemistry, ISSN 0021-9258, E-ISSN 1083-351X, Vol. 394, no 44, p. 15889-15897, article id jbc.RA119.009492Article in journal (Refereed)
    Abstract [en]

    The building blocks of DNA, dNTPs, can be produced de novo or can be salvaged from deoxyribonucleosides. However, to what extent the absence of de novo dNTP production can be compensated for by the salvage pathway is unknown. Here, we eliminated de novo dNTP synthesis in the mouse heart and skeletal muscle by inactivating ribonucleotide reductase (RNR), a key enzyme for the de novo production of dNTPs, at embryonic day 13. All other tissues had normal de novo dNTP synthesis and theoretically could supply heart and skeletal muscle with deoxyribonucleosides needed for dNTP production by salvage. We observed that the dNTP and NTP pools in wild-type postnatal hearts are unexpectedly asymmetric, with unusually high dGTP and GTP levels compared with those in whole mouse embryos or murine cell cultures. We found that RNR inactivation in heart led to strongly decreased dGTP and increased dCTP, dTTP, and dATP pools; aberrant DNA replication; defective expression of muscle-specific proteins; progressive heart abnormalities; disturbance of the cardiac conduction system; and lethality between the second and fourth weeks after birth. We conclude that dNTP salvage cannot substitute for de novo dNTP synthesis in the heart and that cardiomyocytes and myocytes initiate DNA replication despite an inadequate dNTP supply. We discuss the possible reasons for the observed asymmetry in dNTP and NTP pools in wildtype hearts.

  • 39. Von Walden, Ferdinand
    et al.
    Gantelius, Stefan
    Liu, Chang
    Borgström, Hanna
    Björk, Lars
    Gremark, Ola
    Stål, Per
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (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 synthesis2018In: Muscle and Nerve, ISSN 0148-639X, E-ISSN 1097-4598, Vol. 58, no 2, p. 277-285Article in journal (Refereed)
    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.

  • 40.
    Yu, F
    et al.
    Pennsylvania State University.
    Stål, Per
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Thornell, Lars-Eric
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Larsson, L
    Human single masseter muscle fibers contain unique combinations of myosin and myosin binding protein C isoforms2002In: Journal of Muscle Research and Cell Motility, ISSN 0142-4319, E-ISSN 1573-2657, Vol. 23, no 4, p. 317-326Article in journal (Refereed)
    Abstract [en]

    Striated craniofacial and limb muscles differ in their embryological origin, regulatory program during myogenesis, and innervation. In an attempt to explore the effects of these differences on the striated muscle phenotype in humans, the expression of myosin and myosin-associated thick filament proteins were studied at the single fiber level both in the human jaw-closing masseter muscle and in two limb muscles (biceps brachii and quadriceps femoris muscles). In the masseter, unique combinations of myosin heavy chain (MyHC) and myosin binding protein C (MyBP-C) isoforms were observed at the single fiber level. Compared to the limb muscles, the MyHC isoform expression was more complex in the masseter while the opposite was observed for MyBP-C. In limb muscles, a coordinated expression of three MyHC and three MyBP-C isoforms were observed, i.e., single fibers contained one or two MyHC isoforms, and up to three MyBP-C isoforms. Also, the relative content of the different MyBP-C isoforms correlated with the MyHC isoform expression. In the masseter, on the other hand, up to five different MyHC isoforms could be observed in the same fiber, but only one MyBP-C isoform was identified irrespective MyHC isoform expression. This MyBP-C isoform had a migration rate similar to the slow MyBP-C isoform in limb muscle fibers. In conclusion, a unique myofibrillar protein isoform expression was observed in the human masseter muscle fibers, suggesting significant differences in structural and functional properties between muscle fibers from human masseter and limb muscles.

  • 41.
    Yu, Ji-Guo
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Sports Medicine.
    Bonnerud, Patrik
    Department of Health Sciences, Luleå University of Technology, Luleå.
    Eriksson, Anders
    Department of Health Sciences, Luleå University of Technology, Luleå.
    Stål, Per S.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Tegner, Yelverton
    Department of Health Sciences, Luleå University of Technology, Luleå.
    Malm, Christer
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Sports Medicine.
    Effects of long term supplementation of anabolic androgen steroids on human skeletal muscle2014In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 9, no 9, article id e105330Article in journal (Refereed)
    Abstract [en]

    The effects of long-term (over several years) anabolic androgen steroids (AAS) administration on human skeletal muscle are still unclear. In this study, seventeen strength training athletes were recruited and individually interviewed regarding self-administration of banned substances. Ten subjects admitted having taken AAS or AAS derivatives for the past 5 to 15 years (Doped) and the dosage and type of banned substances were recorded. The remaining seven subjects testified to having never used any banned substances (Clean). For all subjects, maximal muscle strength and body composition were tested, and biopsies from the vastus lateralis muscle were obtained. Using histochemistry and immunohistochemistry (IHC), muscle biopsies were evaluated for morphology including fiber type composition, fiber size, capillary variables and myonuclei. Compared with the Clean athletes, the Doped athletes had significantly higher lean leg mass, capillary per fibre and myonuclei per fiber. In contrast, the Doped athletes had significantly lower absolute value in maximal squat force and relative values in maximal squat force (relative to lean body mass, to lean leg mass and to muscle fiber area). Using multivariate statistics, an orthogonal projection of latent structure discriminant analysis (OPLS-DA) model was established, in which the maximal squat force relative to muscle mass and the maximal squat force relative to fiber area, together with capillary density and nuclei density were the most important variables for separating Doped from the Clean athletes (regression  =  0.93 and prediction  =  0.92, p<0.0001). In Doped athletes, AAS dose-dependent increases were observed in lean body mass, muscle fiber area, capillary density and myonuclei density. In conclusion, long term AAS supplementation led to increases in lean leg mass, muscle fiber size and a parallel improvement in muscle strength, and all were dose-dependent. Administration of AAS may induce sustained morphological changes in human skeletal muscle, leading to physical performance enhancement.

  • 42.
    Yu, Ji-Guo
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Sports Medicine.
    Liu, Jing-Xia
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Carlsson, Lena
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Thornell, Lars-Eric
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Stål, Per S
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Re-evaluation of sarcolemma injury and muscle swelling in human skeletal muscles after eccentric exercise2013In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 8, no 4, article id e62056Article in journal (Refereed)
    Abstract [en]

    The results regarding the effects of unaccustomed eccentric exercise on muscle tissue are often conflicting and the aetiology of delayed onset muscle soreness (DOMS) induced by eccentric exercise is still unclear. This study aimed to re-evaluate the paradigm of muscular alterations with regard to muscle sarcolemma integrity and fibre swelling in human muscles after voluntary eccentric exercise leading to DOMS. Ten young males performed eccentric exercise by downstairs running. Biopsies from the soleus muscle were obtained from 6 non-exercising controls, 4 exercised subjects within 1 hour and 6 exercised subjects at 2-3 days and 7-8 days after the exercise. Muscle fibre sarcolemma integrity, infiltration of inflammatory cells and changes in fibre size and fibre phenotype composition as well as capillary supply were examined with specific antibodies using enzyme histochemistry and immunohistochemistry. Although all exercised subjects experienced DOMS which peaked between 1.5 to 2.5 days post exercise, no significant sarcolemma injury or inflammation was detected in any post exercise group. The results do not support the prevailing hypothesis that eccentric exercise causes an initial sarcolemma injury which leads to subsequent inflammation after eccentric exercise. The fibre size was 24% larger at 7-8 days than at 2-3 days post exercise (p<0.05). In contrast, the value of capillary number per fibre area tended to decrease from 2-3 days to 7-8 days post exercise (lower in 5 of the 6 subjects at 7-8 days than at 2-3 days; p<0.05). Thus, the increased fibre size at 7-8 days post exercise was interpreted to reflect fibre swelling. Because the fibre swelling did not appear at the time that DOMS peaked (between 1.5 to 2.5 days post exercise), we concluded that fibre swelling in the soleus muscle is not directly associated with the symptom of DOMS.

1 - 42 of 42
CiteExportLink to result list
Permanent link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf