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  • 1.
    Andersén, Peter
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Bäckström, Torbjörn
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Dahlquist, Gisela
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Damber, Jan-Erik
    Engström-Laurent, Anna
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Gustafson, Yngve
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Geriatrik.
    Hjemdahl, Paul
    Korsgren, Olle
    Olsson, Håkan
    Wiberg, Mikael
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Handkirurgi.
    Widmark, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Svensk medicinsk forskning behöver inte mer styrning2014Ingår i: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 111, nr 22-23, s. 980-981Artikel i tidskrift (Övrig (populärvetenskap, debatt, mm))
  • 2.
    Bertheim, Ulf
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap.
    Engström-Laurent, Anna
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin.
    Hofer, Per-Åke
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Dermatologi och venereologi.
    Hallgren, Peter
    Asplund, Johan
    Hellström, Sten
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Öron- näs- och halssjukdomar.
    Loss of hyaluronan in the basement membrane zone of the skin correlates to the degree of stiff hands in diabetes patients2002Ingår i: Acta Dermato-Venereologica, ISSN 0001-5555, E-ISSN 1651-2057, Vol. 82, nr 5, s. 329-334Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Glycosaminoglycans are important components of all extracellular matrices. One of the glycosaminoglycans is hyaluronan, which is ubiquitously distributed throughout the connective tissue. Hyaluronan is especially abundant in the skin, in which it is of both structural and functional importance. This study describes the localization and distribution of hyaluronan in the skin of healthy individuals and of 23 patients with insulin-dependent diabetes mellitus and various degrees of limited joint mobility. In normal skin, hyaluronan staining was seen in all layers but most prominently in the papillary dermis and the basement membrane zone. In the skin from diabetic patients with normal or only moderately restricted mobility of the hands (limited joint mobility grades 0 and 1), the distribution of hyaluronan was similar to that of normal skin. In the skin of patients with severe restriction in joint mobility (limited joint mobility grade 2) the staining pattern was significantly different with weak hyaluronan staining in the papillary dermis and the basement membrane zone almost devoid of hyaluronan. Moreover, an increased epidermal thickness in the latter patients was evident as well as a pronounced hyaluronan staining compared with normal epidermis.

  • 3.
    Do, Lan
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin. Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk kemi och biofysik.
    Dahl, Christen P
    Kerje, Susanne
    Hansell, Peter
    Mörner, Stellan
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Kardiologi.
    Lindqvist, Ulla
    Engström-Laurent, Anna
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Larsson, Göran
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk kemi och biofysik.
    Hellman, Urban
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    High Sensitivity Method to Estimate Distribution of Hyaluronan Molecular Sizes in Small Biological Samples Using Gas-Phase Electrophoretic Mobility Molecular Analysis.2015Ingår i: International Journal of Cell Biology, ISSN 1687-8876, E-ISSN 1687-8884, artikel-id 938013Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Hyaluronan is a negatively charged polydisperse polysaccharide where both its size and tissue concentration play an important role in many physiological and pathological processes. The various functions of hyaluronan depend on its molecular size. Up to now, it has been difficult to study the role of hyaluronan in diseases with pathological changes in the extracellular matrix where availability is low or tissue samples are small. Difficulty to obtain large enough biopsies from human diseased tissue or tissue from animal models has also restricted the study of hyaluronan. In this paper, we demonstrate that gas-phase electrophoretic molecular mobility analyzer (GEMMA) can be used to estimate the distribution of hyaluronan molecular sizes in biological samples with a limited amount of hyaluronan. The low detection level of the GEMMA method allows for estimation of hyaluronan molecular sizes from different parts of small organs. Hence, the GEMMA method opens opportunity to attain a profile over the distribution of hyaluronan molecular sizes and estimate changes caused by disease or experimental conditions that has not been possible to obtain before.

  • 4.
    Engström-Laurent, Anna
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Nya tag för klinisk forskning: Mycket är på gång för att lösa forskningens nygamla problem2011Ingår i: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 108, nr 3, s. 76-77Artikel i tidskrift (Refereegranskat)
  • 5.
    Engström-Laurent, Anna
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Johansson, Per
    Jacobsson, Lennart
    Lohmander, Stefan
    Palmér, Mats
    Turesson, Carl
    Wallensten, Richard
    [More equal care with new guidelines for musculoskeletal disorders].2012Ingår i: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 109, nr 22, s. 1102-Artikel i tidskrift (Refereegranskat)
  • 6.
    Hellman, Urban
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin.
    Engström-Laurent, Anna
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin.
    Larsson, Anders
    Lindqvist, Ulla
    Hyaluronan concentration and molecular mass in psoriatic arthritis: biomarkers of disease severity, resistance to treatment, and outcome2019Ingår i: Scandinavian Journal of Rheumatology, ISSN 0300-9742, E-ISSN 1502-7732Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective: Low molecular mass hyaluronan causes inflammatory processes and can act as a pro-inflammatory cytokine in skin and other sites of activity in psoriatic arthritis (PsA). This study investigated whether the molecular mass distribution of hyaluronan (HA) in skin and the quantity of circulating HA are related to the clinical inflammatory picture in PsA with active disease and to the effect of treatment with anti-tumour necrosis factor-α (anti-TNF-α) adalimumab.

    Methods: Twenty patients with TNF-α-naïve active polyarticular PsA were included in this prospective clinical trial of treatment with 40 mg s.c. adalimumab according to standard procedure. Clinical activity, patients’ assessments, and skin biopsies were captured at inclusion and at the 12 week follow-up. Ten healthy individuals were recruited for comparison of HA analyses. Histochemistry of skin inflammation, serum HA, and molecular mass of HA were determined.

    Results: Overall improvements in clinical parameters were observed. Eight of 18 patients reached minimum disease activity after 12 weeks and disease activity was significantly reduced (p < 0.0001). Patients with elevated serum HA values were significantly older, had later onset of arthritis and more deformed joints, still had swollen joints after treatment, and had more circulating inflammatory biomarkers. More severe disease pathology showed a wide spectrum of high-molecular-mass HA accompanied by low mass HA. The treatment appears partly to normalize the HA mass distribution.

    Conclusion: HA concentration and mass seem to be two possible factors in the inflammatory pathology of PsA acting as biomarkers for disease severity, resistance to treatment, and worse outcome.

  • 7.
    Hellman, Urban
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin. Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Medicinsk och klinisk genetik.
    Hellström, Martin
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Mörner, Stellan
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Engström Laurent, Anna
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Aberg, Anna-Maja
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin. Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Anestesiologi och intensivvård.
    Oliviero, Patricia
    Samuel, Jane-Lise
    Waldenström, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Parallel up-regulation of FGF-2 and hyaluronan during development of cardiac hypertrophy in rat2008Ingår i: Cell and Tissue Research, ISSN 0302-766X, E-ISSN 1432-0878, Vol. 332, nr 1, s. 49-56Artikel i tidskrift (Refereegranskat)
  • 8.
    Hellman, Urban
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Malm, Linus
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk kemi och biofysik.
    Ma, Li-Ping
    Larsson, Göran
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk kemi och biofysik.
    Mörner, Stellan
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Fu, Michael
    Engström-Laurent, Anna
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Waldenström, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Growth factor PDGF-BB stimulates cultured cardiomyocytes to synthesize the extracellular matrix component hyaluronan2010Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 5, nr 12, s. e14393-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Co-cultivation of cardiomyocytes and fibroblasts (80%/20%) increased HA concentration far more that can be explained by HA synthesis by the two cell types separately, revealing a crosstalk between cardiomyocytes and fibroblasts that induces HA synthesis. We conclude that dynamic changes of the myocardium, such as in cardiac hypertrophy, do not depend on the cardiomyocyte alone, but are achieved when both cardiomyocytes and fibroblasts are present.

  • 9.
    Hellman, Urban
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Malm, Linus
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk kemi och biofysik.
    Ma, Li-Ping
    Larsson, Göran
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk kemi och biofysik.
    Mörner, Stellan
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Kardiologi.
    Fu, Michael
    Engström-Laurent, Anna
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Waldenström, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Kardiologi.
    Hyaluronan is both a product and stimulator of cardiomyocytes: a study in cell cultures of cardiomyocytes and fibroblastsArtikel i tidskrift (Refereegranskat)
  • 10.
    Hellman, Urban
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Mörner, Stellan
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Engström-Laurent, Anna
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Samuel, Jane-Lise
    Waldenström, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Temporal correlation between transcriptional changes and increased synthesis of hyaluronan in experimental cardiac hypertrophy2010Ingår i: Genomics, ISSN 0888-7543, E-ISSN 1089-8646, Vol. 96, nr 2, s. 73-81Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The role of hyaluronan in cardiac growth has become evident, previously shown by increased myocardial levels of hyaluronan in a rat model of cardiac hypertrophy. To further investigate the role of hyaluronan and regulation of its synthesis in cardiac hypertrophy, quantitative measurements of myocardial hyaluronan concentration was correlated to gene transcription in hypertrophic cardiac tissue. Factor analysis was used to study this correlation over time. A subset of differentially expressed genes was identified with a transcriptional regulation correlating to the increased synthesis of hyaluronan, suggesting a common regulatory pathway. Four transcription factors, Myc, Fos, Junb and Egr1, were also up-regulated. Furthermore, the Ace gene was up-regulated, representing increase of angiotensin II, an inducer of these transcription factors and fetal genes in cardiac hypertrophy. This demonstrates a coordinated synthesis of hyaluronan and pro-hypertrophic gene expression, regulated by immediate early genes, with angiotensin II as a possible mediator.

  • 11.
    Hellström, Martin
    et al.
    Umeå universitet, Medicinsk fakultet, Folkhälsa och klinisk medicin. Umeå universitet, Medicinsk fakultet, Klinisk vetenskap, Öron- näs- och halssjukdomar.
    Engström Laurent, Anna
    Umeå universitet, Medicinsk fakultet, Folkhälsa och klinisk medicin. Umeå universitet, Medicinsk fakultet, Klinisk vetenskap, Öron- näs- och halssjukdomar.
    Hellström, Sten
    Umeå universitet, Medicinsk fakultet, Klinisk vetenskap, Öron- näs- och halssjukdomar.
    Expression of the CD44 receptor in the blood vessel system: an experimental study in rat.2005Ingår i: Cells Tissues Organs, ISSN 1422-6405, E-ISSN 1422-6421, Vol. 179, nr 3, s. 102-108Artikel i tidskrift (Refereegranskat)
  • 12.
    Hellström, Martin
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin. Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Engström-Laurent, Anna
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Mörner, Stellan
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Kardiologi.
    Johansson, Bengt
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Kardiologi.
    Hyaluronan and collagen in human hypertrophic cardiomyopathy: a morphological analysis2012Ingår i: Cardiology Research and Practice, ISSN 2090-8016, E-ISSN 2090-0597, Vol. 2012, s. 545219-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The hypertrophic cardiomyopathy (HCM) disease process is not only limited to cardiomyocyte abnormalities but also engages the extracellular matrix. Hyaluronan (HA) and its receptor CD44 are involved in cellular growth and tissue proliferation but have so far been less studied in myocardial hypertrophy. In HCM, collagens are abundant but their histological distribution and relation to hyaluronan have not been described. Material and Methods. Myocardial specimens from 5 patients with symptomatic left ventricular tract obstruction undergoing myectomy due to HCM were processed for histochemistry and immunohistochemistry. Results. HA staining was more intense in HCM patients. The histological distribution of HA was the same in patients and controls, that is, interstitial staining including the space between cardiomyocytes, in fibrous septa, and in the adventitia of intramyocardial blood vessels. CD44 was not detected in the myocardium of patients or controls. Collagen I showed the same general localisation as HA but detailed distribution differed. Conclusions. This is the first study that describes the distribution of hyaluronan in human HCM. HA staining is more intense in HCM patients but without coexpression of its receptor CD44, at least not in the chronic phase of HCM. HA and collagen I have the same localisation.

  • 13.
    Hellström, Martin
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Hellström, Sten
    Department of Audiology and Neurotology, Karolinska University Hospital, Stockholm, Sweden.
    Engström-Laurent, Anna
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Bertheim, Ulf
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap.
    The structure of the basement membrane zone differs between keloids, hypertrophic scars and normal skin: A possible background to an impaired function2014Ingår i: Journal of Plastic, Reconstructive & Aesthetic Surgery, ISSN 1748-6815, E-ISSN 1532-1959, Vol. 67, nr 11, s. 1564-1572Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Scar tissues were collected from patients with keloids, hypertrophic scars and mature scars. Normal skin was obtained from healthy individuals. Clinical attributes were used to select which tissue to obtain but the distribution of the specific hyaluronan (HA) staining was then used for the definite classification of the various scar types. Light microscopic and ultrastructural analyses were performed with an HA-binding probe, antibodies for collagen I and III and staining for mast cells. Ultrastructural studies of keloids revealed an altered collagen structure in the dermal layers, with an abundance of collagen fibres of similar diameter in both the reticular dermis (RD) and the papillary dermis (PD) compared to normal skin. Furthermore, the keloids displayed epidermal changes, which involved the basement membrane (BM), with fewer hemidesmosomes and an altered shape of desmosomes in the entire enlarged spinous layer. The frequency of mast cells found in keloids was lower than in other scar tissues and normal skin. These alterations in epidermis could influence the hydrodynamic and cell regulatory properties of the wounded skin with impaired function and insufficient regulative capacity to hinder the ever-growing collagen tissue that is characteristic for keloids. (C) 2014 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.

  • 14.
    Hellström, Martin
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Johansson, Bengt
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Engström Laurent, Anna
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Hyaluronan and its receptor CD44 in the heart of newborn and adult rats.2006Ingår i: Anatomical record part A: discoveries in molecular, cellular, and evolutionary biology, ISSN 1552-4884, Vol. 288, nr 6, s. 587-592Artikel i tidskrift (Refereegranskat)
  • 15.
    Hultdin, Magnus
    et al.
    Umeå universitet, Medicinsk fakultet, Medicinsk biovetenskap, Patologi.
    Sundström, Gunnel
    Umeå universitet, Medicinsk fakultet, Folkhälsa och klinisk medicin, Medicin.
    Wahlin, Anders
    Umeå universitet, Medicinsk fakultet, Folkhälsa och klinisk medicin, Medicin.
    Lundström, Berith
    Umeå universitet, Medicinsk fakultet, Folkhälsa och klinisk medicin, Medicin.
    Samuelsson, Jan
    Birgegård, Gunnar
    Engström Laurent, Anna
    Umeå universitet, Medicinsk fakultet, Folkhälsa och klinisk medicin, Medicin.
    Progression of bone marrow fibrosis in patients with essential thrombocythemia and polycythemia vera during anagrelide treatment.2007Ingår i: Med Oncol, ISSN 1357-0560, Vol. 24, nr 1, s. 63-70Artikel i tidskrift (Refereegranskat)
  • 16.
    Johansson, Bengt
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Kardiologi.
    Holmgren, Anders
    Hedström, Magnus
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Kardiologi.
    Engström-Laurent, Anna
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Engström, Karl Gunnar
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Kirurgi.
    Evaluation of hyaluronan and calcifications in stenotic and regurgitant aortic valves.2011Ingår i: European Journal of Cardio-Thoracic Surgery, ISSN 1010-7940, E-ISSN 1873-734X, Vol. 39, nr 1, s. 27-32Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective: Hyaluronan (HA) is a major component of the interstitium and has been observed in normal heart valves. The function of HA in heart valves is unknown but contribution to biomechanical function has been proposed. The purpose of this investigation was to study the distribution of HA in relation to calcifications in diseased human aortic valves. Methods: Human aortic valves were collected at aortic valve replacement, of whom nine patients had regurgitation and 13 stenotic disease. The valves were decalcified and stained for the visualisation of HA. The specimens were macroscopically evaluated for magnitude of calcification using image analysis. The microscopic amount and distribution of HA and calcifications were semiquantitatively evaluated using histochemistry. Results: The overall HA staining showed an inverse relationship against the magnitude of observed valve calcifications (p<0.001) and type of disease (p=0.014). Multiple-group comparison revealed regionally reduced HA staining in diffuse and heavy calcified regions inside the valve (both p<0.001) compared with normal-structured parts of the valve. HA was concentrated on the ventricular side of the valve (p=0.002). Conclusions: The content of HA was reduced in calcified aortic valves and had a heterogeneous distribution, potentially contributing to poor valve function. HA may also be involved in the pathophysiological process in degenerative aortic stenosis.

  • 17.
    Josefsson, Andreas
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Adamo, Hani
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Hammarsten, Peter
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Granfors, Torvald
    Stattin, Pär
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Urologi och andrologi.
    Egevad, Lars
    Laurent, Anna Engström
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Wikström, Pernilla
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Bergh, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Prostate cancer increases hyaluronan in surrounding nonmalignant stroma, and this response is associated with tumor growth and an unfavorable outcome2011Ingår i: American Journal of Pathology, ISSN 0002-9440, E-ISSN 1525-2191, Vol. 179, nr 4, s. 1961-1968Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Our objective was to investigate whether the presence of a tumor increases hyaluronan (HA) levels in surrounding prostate tissues and whether this extratumoral HA influences tumor growth and outcome. From a series of 287 men diagnosed with prostate cancer at transurethral resection and followed up with watchful waiting, tissue microarrays were constructed, stained, and scored for HA. A high HA staining score in the tumor stroma or in nonmalignant prostate tissue stroma were both associated positively with higher Gleason score and larger tumor volume, and was associated with a poor outcome. HA staining score was not an independent marker for outcome (multivariate Cox, with Gleason score, tumor volume, stage, and HA variables). In an orthotopic rat prostate cancer model, hyaluronic acid synthase-1 mRNA levels and HA staining were increased in normal prostate tissue surrounding prostate cancer. Orthotopic prostate cancer growth was increased by intraprostatic injection of HA. In conclusion, cancer in the prostate apparently stimulates HA synthesis both in tumor stroma and in the surrounding normal tissue. This promoted tumor growth and was associated with an unfavorable outcome.

  • 18. Kerje, Susanne
    et al.
    Hellman, Urban
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Do, Lan
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk kemi och biofysik.
    Larsson, Göran
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk kemi och biofysik.
    Kämpe, Olle
    Engström-Laurent, Anna
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Lindqvist, Ulla
    Is low molecular hyaluronan an early indicator of disease in avian systemic sclerosis?2016Ingår i: Connective Tissue Research, ISSN 0300-8207, E-ISSN 1607-8438, Vol. 57, nr 5, s. 337-346Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    AIM OF THE STUDY: To further elucidate the pathogenesis of systemic sclerosis (SSc) an experimental avian model was used. University of California at Davies line 200-chicken (UCD-200) spontaneously develops a SSc like disease that has most features of human SSc with vascular effects, inflammation, autoimmunity and fibrosis. The first signs of disease in UCD-200 are swelling and ischemic lesions of the comb, a tissue containing high amounts of the glycosaminoglycan hyaluronan. The aim was to evaluate inflammatory and fibrotic processes of the disease with regard to the molecular weight of hyaluronan.

    MATERIAL AND METHODS: Comb biopsies from UCD-200 and healthy White Leghorn (WL) chickens as controls at different ages were studied with histochemical localization of hyaluronan, hyaluronidase 1, CD3, IgY and collagen I and III. Hyaluronan molecular weight distribution was estimated with gas phase electrophoretic analysis.

    RESULTS: At 2 days of age hyaluronan was visualized in UCD-200 at the dermal part of the comb with no simultaneous staining of Hyal-1. In adult UCD-200 the comb skin was almost totally devoid of hyaluronan compared to WL of the same age. An increase of low molecular weight (LMW) hyaluronan was detected in comb tissue from UCD-200 at 1 day, 1, 2, 4 weeks in contrast to adult animals.

    CONCLUSIONS: An early inflammatory process involving LMW hyaluronan was confirmed as a possible profibrotic process. This indicates that hyaluronan might be an important participant in early inflammatory events of SSc in UCD-200 chicken and that disappearance of hyaluronan in skin predisposes to fibrosis.

  • 19. Lindqvist, Ulla
    et al.
    Pihl-Lundin, Inger
    Engström Laurent, Anna Margareta
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Dermal Distribution of Hyaluronan in Psoriatic Arthritis: Coexistence of CD44, MMP3 and MMP92012Ingår i: Acta Dermato-Venereologica, ISSN 0001-5555, E-ISSN 1651-2057, Vol. 92, nr 4, s. 372-377Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Psoriatic arthritis is a chronic systemic disease in which patients develop persistent inflammation of the skin and joints, leading to disability and joint damage. The extracellular component hyaluronan (HA) plays an important role in regulatory processes such as inflammation, wound healing and tumour progression. At any site of inflammation HA can be depolymerized to low-molecular weight fragments, which, in turn, induce an array of inflammatory mediators that can lead to chronic inflammation. This study describes the serum concentration and dermal distribution of HA, its receptor CD44 and the metalloproteinases 3 and 9 in skin biopsies from patients with different types of psoriatic arthritis. Fifty-one patients with psoriatic arthritis were included in the study and classified as oligo- or poly-arthritic PsA with and without treatment. Biopsies were obtained from both involved and non-involved skin and compared with biopsies from healthy individuals. Serum HA was analysed for estimation of the total turnover of HA. The main findings were an overall redistribution of HA in both involved and non-involved psoriatic skin and an epidermal imbalance between HA and CD44. The structurally and functionally important basement membrane zone was found to be disintegrated and devoid of HA irrespective of the type of articular involvement, treatment or skin affection.

  • 20. Opheim, Leif Runar
    et al.
    Hellman, Urban
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Engström-Laurent, Anna
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Laurent, Claude
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Öron- näs- och halssjukdomar. Department of Speech/Language Pathology and Audiology, University of Pretoria, Pretoria, South Africa.
    Hyaluronan in Human Vocal Folds in Smokers and Nonsmokers: A Histochemical Study2016Ingår i: Journal of Voice, ISSN 0892-1997, E-ISSN 1873-4588, Vol. 30, nr 3, s. 255-262Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVES/HYPOTHESIS: To study the hyaluronan occurrence in human vocal folds, with special regards to gender and smoking and to discuss the implications of findings.

    STUDY DESIGN: This is a descriptive/morphologic study.

    METHODS: Sixteen cadaveric vocal folds from eight individuals between 58 and 90 years old (six women and two men) were removed and studied morphologically. Three of the individuals had been cigarette smokers. A direct method for hyaluronan histochemistry using a hyaluronan-binding protein probe (HABP) was used to visualize the polysaccharide. Five examiners performed an analysis of the intensities of hyaluronan staining, independently.

    RESULTS: We observed intense hyaluronan staining of the vocal folds of which those from women stained considerably stronger than those from men. Stratified squamous epithelium stained for hyaluronan in all sections, whereas respiratory epithelium only stained weakly or not at all. The highest accumulation of hyaluronan occurred subepithelially in the lamina propria, corresponding to Reinke's space. It was observed that vocal folds from smokers were more intensively stained than those from nonsmokers.

    CONCLUSIONS: Hyaluronan is found in all layers of the human vocal fold. Contradictory to earlier studies, hyaluronan was visualized in squamous epithelium, where it may function as an impact protector. The occurrence of hyaluronan in smokers may have implications in the development of vocal fold inflammation and tumor initiation as hyaluronan is an important molecule in these processes.

  • 21.
    Sundström, Gunnel
    et al.
    Umeå universitet, Medicinsk fakultet, Folkhälsa och klinisk medicin, Medicin.
    Dahl, Inger Marie S
    Hultdin, Magnus
    Umeå universitet, Medicinsk fakultet, Medicinsk biovetenskap, Patologi.
    Lundström, Berit
    Umeå universitet, Medicinsk fakultet, Klinisk vetenskap, Öron- näs- och halssjukdomar.
    Wahlin, Anders
    Umeå universitet, Medicinsk fakultet, Folkhälsa och klinisk medicin, Medicin.
    Engström Laurent, Anna
    Umeå universitet, Medicinsk fakultet, Folkhälsa och klinisk medicin, Medicin.
    Bone marrow hyaluronan distribution in patients with acute myeloid leukemia.2005Ingår i: Medical Oncology, ISSN 1357-0560, E-ISSN 1559-131X, Vol. 22, nr 1, s. 71-78Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The present study investigated potential age-related changes in human muscle spindles with respect to the intrafusal fiber-type content and myosin heavy chain (MyHC) composition in biceps brachii muscle. The total number of intrafusal fibers per spindle decreased significantly with aging, due to a significant reduction in the number of nuclear chain fibers. Nuclear chain fibers in old spindles were short and some showed novel expression of MyHC α-cardiac. The expression of MyHC α-cardiac in bag1 and bag2 fibers was greatly decreased in the A region. The expression of slow MyHC was increased in nuclear bag1 fibers and that of fetal MyHC decreased in bag2 fibers whereas the patterns of distribution of the remaing MyHC isoforms were generelly not affected by aging. We conclude that aging appears to have an important impact on muscle spindle composition. These changes in muscle spindle phenotype may reflect an age-related deterioration in sensory and motor innervation and are likely to have an impact in motor control in the elderly.

  • 22.
    Sundström, Gunnel
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Hultdin, Magnus
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Engström-Laurent, Anna
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Dahl, IMS
    Bone marrow hyaluronan and reticulin in patients with malignant disorders2010Ingår i: Medical Oncology, ISSN 1357-0560, E-ISSN 1559-131X, Vol. 27, nr 3, s. 618-623Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Myelofibrosis is commonly seen in patients with chronic myeloproliferative diseases and sometimes in myelodysplastic syndrome, acute leukaemia and lymphoproliferative diseases. The fibrotic process is evaluated by grading the amount of collagen deposited in the bone marrow interstitium. The established method to evaluate bone marrow fibrosis is staining for reticulin to visualise the collagen fibres. However, the extra cellular matrix does not only contain collagens but also other components, e.g. glycosaminoglycans of which hyaluronan is the most abundant. Hyaluronan is important for structural and cellular functions. Earlier studies have shown that there is a positive correlation between hyaluronan and reticulin staining in healthy volunteers and in patients with de novo acute myeloid leukaemia. In this study bone marrow biopsies from 43 patients with a malignant disease involving the bone marrow were compared with 18 patients with a malignant disease not involving the bone marrow. The intensity of hyaluronan grading was significantly higher in the patients with disease involving the bone marrow compared to the healthy controls but not compared to the patients without disease involving the bone marrow. The staining intensity of reticulin in the bone marrow was significantly higher in the patients with disease involving the bone marrow, compared to those without disease involving the bone marrow and to the controls. In all patients and the controls there was a correlation between hyaluronan and reticulin.

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