| 1. |
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| 2. |
- Hellman, Urban, 1966-, et al.
(author)
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Presence of hyaluronan in lung alveoli in severe Covid-19 : an opening for new treatment options?
- 2020
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In: Journal of Biological Chemistry. - : American Society for Biochemistry and Molecular Biology. - 0021-9258 .- 1083-351X. ; 295:45, s. 15418-15422
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Journal article (peer-reviewed)abstract
- Severe corona virus disease 2019 (Covid-19) is characterized by inflammation of the lungs with increasing respiratory impairment. In fatal Covid-19, lungs at autopsy have been filled with a clear liquid jelly. However, the nature of this finding has not yet been determined.The aim of the study was to demonstrate if the lungs of fatal Covid-19 contain hyaluronan as it is associated with inflammation and acute respiratory distress syndrome (ARDS) and may have the appearance of liquid jelly.Lung tissue obtained at autopsy from three deceased Covid-19 patients was processed for hyaluronan histochemistry using a direct staining method and compared with staining in normal lung tissue.Stainings confirmed that hyaluronan is obstructing alveoli with presence in exudate and plugs, as well as in thickened perialveolar interstitium. In contrast, normal lungs only showed hyaluronan in intact alveolar walls and perivascular tissue. This is the first study to confirm prominent hyaluronan exudates in the alveolar spaces of Covid-19 lungs, supporting the notion that the macromolecule is involved in ARDS caused by SARS-CoV-2. The present finding may open up for new treatment options in severe Covid-19, aiming at reducing the presence and production of hyaluronan in the lungs.
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| 3. |
- Johansson, Bengt, et al.
(author)
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Evaluation of hyaluronan and calcifications in stenotic and regurgitant aortic valves.
- 2011
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In: European Journal of Cardio-Thoracic Surgery. - : Elsevier. - 1010-7940 .- 1873-734X. ; 39:1, s. 27-32
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Journal article (peer-reviewed)abstract
- 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.
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| 4. |
- Opheim, Leif Runar, et al.
(author)
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Hyaluronan in Human Vocal Folds in Smokers and Nonsmokers : A Histochemical Study
- 2016
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In: Journal of Voice. - : Elsevier BV. - 0892-1997 .- 1873-4588. ; 30:3, s. 255-262
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Journal article (peer-reviewed)abstract
- 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.
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| 5. |
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| 6. |
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| 7. |
- Bertheim, Ulf, et al.
(author)
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Loss of hyaluronan in the basement membrane zone of the skin correlates to the degree of stiff hands in diabetes patients
- 2002
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In: Acta Dermato-Venereologica. - : Medical Journals Sweden AB. - 0001-5555 .- 1651-2057. ; 82:5, s. 329-334
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Journal article (peer-reviewed)abstract
- 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.
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| 8. |
- Do, Lan, et al.
(author)
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High Sensitivity Method to Estimate Distribution of Hyaluronan Molecular Sizes in Small Biological Samples Using Gas-Phase Electrophoretic Mobility Molecular Analysis.
- 2015
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In: International Journal of Cell Biology. - : Hindawi Limited. - 1687-8876 .- 1687-8884.
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Journal article (peer-reviewed)abstract
- 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.
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| 9. |
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| 10. |
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| 11. |
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| 12. |
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| 13. |
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| 14. |
- Hellman, Urban, 1966-
(author)
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About hyaluronan in the hypertrophic heart : studies on coordinated regulation of extracellular matrix signalling
- 2010
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Doctoral thesis (other academic/artistic)abstract
- Background. Myocardial hypertrophy is a risk factor for cardiovascular morbidity and mortality. Independent of underlying disease, the cardiac muscle strives in different ways to compensate for an increased workload. This remodelling of the heart includes changes in the extracellular matrix which will affect systolic and diastolic cardiac function. Furthermore, signal transduction, molecular diffusion and microcirculation will be affected in the hypertrophic process. One important extracellular component is the glycosaminoglycan hyaluronan. It has been shown to play a major role in other conditions that feature cellular growth and proliferation, such as wound healing and malignancies. The aim of this thesis was to investigate hyaluronan and its role in both an experimental rat model of cardiac hypertrophy as well as in cultured mouse cardiomyocytes and fibroblasts. Methods. Cardiac hypertrophy was induced in rats by aortic ligation. Hyaluronan concentration was measured and expression of genes coding for hyaluronan synthases were quantified after 1, 6 and 42 days after operation, in cardiac tissue from the left ventricular wall. Localization of hyaluronan and its receptor CD44 was studied histochemically. Hyaluronan synthesis was correlated to gene transcription using microarray gene expression analysis. Cultures of cardiomyocytes and fibroblasts were stimulated with growth factors. Hyaluronan concentration was measured and expression of genes coding for hyaluronan synthases were detected. Hyaluronan size was measured and crosstalk between cardiomyocytes and fibroblasts was investigated. Results. Increased concentration of hyaluronan in hypertrophied cardiac tissue was observed together with an up-regulation of two hyaluronan synthase genes. Hyaluronan was detected in the myocardium and in the adventitia of cardiac arteries whereas CD44 staining was mainly found in and around the adventitia. Hyaluronan synthesis correlated to the expression of genes, regulated by transcription factors known to initiate cardiac hypertrophy. Stimulation of cardiomyocytes by PDGF-BB induced synthesis of hyaluronan. Cardiomyocytes also secreted a factor into culture media that after transfer to fibroblasts initiated an increased synthesis of hyaluronan. When stimulated with hyaluronan of different sizes, a change in cardiomyocyte gene expression was observed. Different growth factors induced production of different sizes of hyaluronan in fibroblasts. The main synthase detected was hyaluronan synthase-2. Cardiomyocytes were also shown to secrete microvesicles containing both DNA and RNA. Isolated microvesicles incubated with fibroblasts were observed by confocal microscopy to be internalized into fibroblasts. Altered gene expression was observed in microvesicle stimulated fibroblasts. Conclusion. This study shows that increased hyaluronan synthesis in cardiac tissue during hypertrophic development is a part of the extracellular matrix remodelling. Cell cultures revealed the ability of cardiomyocytes to both synthesize hyaluronan and to convey signals to fibroblasts, causing them to increase hyaluronan synthesis. Cardiomyocytes are likely to express receptors for hyaluronan, which mediate intracellular signalling causing the observed altered gene expression in cardiomyocytes stimulated with hyaluronan. This demonstrates the extensive involvement of hyaluronan in cardiac hypertrophy.
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| 15. |
- Hellman, Urban, et al.
(author)
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Growth Factor PDGF-BB Stimulates Cultured Cardiomyocytes to Synthesize the Extracellular Matrix Component Hyaluronan.
- 2010
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In: PloS one. - : Public Library of Science (PLoS). - 1932-6203. ; 5:12
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Journal article (peer-reviewed)abstract
- Hyaluronan (HA) is a glycosaminoglycan located in the interstitial space which is essential for both structural and cell regulatory functions in connective tissue. We have previously shown that HA synthesis is up-regulated in a rat model of experimental cardiac hypertrophy and that cardiac tissue utilizes two different HA synthases in the hypertrophic process. Cardiomyocytes and fibroblasts are two major cell types in heart tissue. The fibroblasts are known to produce HA, but it has been unclear if cardiomyocytes share the same feature, and whether or not the different HA synthases are activated in the different cell types.
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| 16. |
- Hellman, Urban, 1966-, et al.
(author)
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Hyaluronan concentration and molecular mass in psoriatic arthritis : biomarkers of disease severity, resistance to treatment, and outcome
- 2019
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In: Scandinavian Journal of Rheumatology. - : Taylor & Francis Group. - 0300-9742 .- 1502-7732. ; 48:4, s. 284-293
-
Journal article (peer-reviewed)abstract
- 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.
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| 17. |
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| 18. |
- Hellman, Urban, 1966-, et al.
(author)
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Temporal correlation between transcriptional changes and increased synthesis of hyaluronan in experimental cardiac hypertrophy
- 2010
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In: Genomics. - : Elsevier BV. - 0888-7543 .- 1089-8646. ; 96:2, s. 73-81
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Journal article (peer-reviewed)abstract
- 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.
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| 19. |
- Hellström, Martin, et al.
(author)
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Expression of the CD44 receptor in the blood vessel system : an experimental study in rat.
- 2005
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In: Cells Tissues Organs. - : S. Karger AG. - 1422-6405 .- 1422-6421. ; 179:3, s. 102-108
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Journal article (peer-reviewed)abstract
- The CD44 receptor is a transmembrane glycoprotein expressed on a variety of cells like endothelial, epithelial and smooth muscle cells. This molecule has many important functions, e.g. in cell-cell and cell-matrix interactions and signal transduction. The main ligand for CD44 is hyaluronan (HYA). HYA is a glycosaminoglycan with structural and cell biological properties. The localization of HYA in the vessel wall of arteries and veins in the healthy adult and newborn rat has been described earlier. In this study the occurrence of the CD44 receptor was investigated in the same vessels and compared to the localization of HYA. Both CD44 and its ligand showed an increased expression in the vessel wall of newborn rats compared to that of adult rats. Although HYA is abundant in the adventitia of adult rats, virtually no expression of CD44 was observed. Our results indicate that the CD44 receptor expression is increased during the stage of maturation of the vessel tree whereas the CD44 receptor is less needed by HYA in the healthy vessel wall.
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| 20. |
- Hellström, Martin, et al.
(author)
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Hyaluronan and collagen in human hypertrophic cardiomyopathy : a morphological analysis
- 2012
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In: Cardiology Research and Practice. - : Hindawi Limited. - 2090-8016 .- 2090-0597. ; 2012, s. 545219-
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Journal article (peer-reviewed)abstract
- 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.
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| 21. |
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| 22. |
- Hellström, Martin, 1979-
(author)
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Hyaluronan and the receptor CD 44 in the heart and vessels : a study in normal and pathological conditions
- 2007
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Doctoral thesis (other academic/artistic)abstract
- Tissues are not solely composed of cells. The extracellular matrix is important for the cell well-being and cell-cell communication. The glycosaminoglycan hyaluronan (HYA) is a widely distributed extracellular matrix (ECM) component. The molecule has prominent physicochemical properties, foremost viscoelastic and osmotic, but participates in many biological processes such as cell migration, proliferation, tissue turnover, wound healing and angiogenesis. HYA is synthesised by either of three different hyaluronan-synthesising enzymes, HAS1-3, and its main ligand is the transmembrane receptor CD44. In the heart and vessels the matrix components are of great importance for endurance and elasticity which are prerequisites for a normal function. The aims of the study were to describe the distribution of HYA and its receptor CD44 in normal cardiovascular tissue and to investigate the ECM composition in myocardial hypertrophy. Normal conditions were studied in a rat model. These studies showed that the tunica adventitia in almost all vessels stained strongly for HYA. The expression in the tunica intima and media on the venous side, differed between the vessels and was almost absent on the arterial side. In the adult animals only minute amounts of CD44 were detected. The expression of both HYA and CD44 was increased in newborn rats. In the heart HYA was unevenly distributed in the interstitium. Strong HYA-staining was seen in the valves and in the adventitia of intramyocardial vessels. Almost no CD44-staining was observed. Notably, there was no obvious difference between newborn and adult animals. In an experimental rat model of pressure-induced cardiac hypertrophy the mRNA-levels of HAS1, HAS2, CD44, basic Fibroblast Growth Factor (FGF-2) and Fibroblast Growth Factor Receptor-1 (FGFR-1) were elevated on day 1 after aortic banding. HAS2, CD44 and FGFR-1 were at basal levels on day 42. The HYA-concentration was significally elevated on day 1. HYA was detected in the interstitium by histochemistry and CD44 was detected mainly in and around the intramyocardial vessels. The HYA-staining was increased in myectomi specimens from patients with HCM compared to controls. HYA was detected in the interstitium, in fibrous septas and in the adventitia of intramyocardial vessels. No CD44 was detected in HCM or in control specimens. Our results indicate that HYA and CD44 play an active role in the maturing vessel tree and that the ECM content of HYA is increased in experimental myocardial hypertrophy and human hypertrophic cardiomyopathy.
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| 23. |
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| 24. |
- Hellström, Martin, et al.
(author)
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Hyaluronan is differently located in arteries and veins : an immunohistochemical study in the rat
- 2003
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In: Cells Tissues Organs. - : S. Karger AG. - 1422-6405 .- 1422-6421. ; 173:4, s. 227-233
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Journal article (peer-reviewed)abstract
- The matrix components of the vessel wall are of great importance for the function of the vessel system of which both endurance and elasticity are prerequisites. One component of the vessel wall is the glycosaminoglycan hyaluronan (HYA) with its unique physico-chemical properties, e.g. viscoelasticity and barrier function. The present study aimed to map and compare the normal localisation and distribution of hyaluronan in the arteries and veins of both adult and newborn rats, using a specific staining method utilizing a hyaluronan-binding protein. The hyaluronan stained clearly different in veins and arteries both in newborn and adult rats. In the veins, the tunica intima stained intensely whereas the corresponding area in the arteries only showed a weak and scattered staining pattern. In the adult rats, the matrix between the smooth muscle cells of the tunica media of the veins had a clearly positive staining pattern compared to the media in the arteries which showed only a few scattered areas of positive staining. In the newborn rats, the media of the arteries stained more intensely. In both newborn and adult rats, the adventitia stained intensely both in veins and arteries. Moreover, the HYA-staining pattern differed in veins in different regions of the body. Since HYA is known to be involved in many different biological processes, the results are of importance to understand physiological properties of the vessel tree and to explain the development of vascular diseases.
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| 25. |
- Hellström, Martin, et al.
(author)
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The structure of the basement membrane zone differs between keloids, hypertrophic scars and normal skin : A possible background to an impaired function
- 2014
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In: Journal of Plastic, Reconstructive & Aesthetic Surgery. - : Elsevier BV. - 1748-6815 .- 1878-0539. ; 67:11, s. 1564-1572
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Journal article (peer-reviewed)abstract
- 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.
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| 26. |
- Hillerdal, Gunnar, et al.
(author)
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Hyaluronan in pleural effusions and in serum
- 1991
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In: Cancer. - 0008-543X .- 1097-0142. ; 67:9, s. 2410-2414
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Journal article (peer-reviewed)abstract
- It has been suggested that a high level of hyaluronan (hyaluronic acid, HYA) in pleural fluid is an indicator of malignant mesothelioma. In 78 consecutive patients with pleural effusion of various causes the HYA concentration was measured in pleural fluid samples and in serum. Nine patients had malignant pleural mesothelioma, and in three of them the HYA level in pleural fluid was 100 mg/l or more. In 42 patients with effusions due to metastatic malignancy, the mean HYA in the pleural fluid was 75 mg/l, and in five the HYA level was above 100 mg/l. Cardiac insufficiency caused the effusion in 11 patients, of whom two had a level above 100 mg/l in pleural fluid. Four patients had a serologically confirmed viral infection and had HYA levels in pleural fluid of 8, 157, 335, and 554 mg/l, respectively. One patient had postinfectious effusion with an HYA level in pleural exudate of 748 mg/l, the highest in this investigation. Two patients had benign asbestos pleural effusions, and both had high pleural HYA levels (256 and 490 mg/l, respectively). The serum HYA values were much lower than in the pleural fluid, namely from 15 to 480 micrograms/l; the levels were independent of the levels in the pleural fluid. Thus, a high level of HYA in pleural fluid is not specific for mesothelioma but can occur in other malignant or benign diseases, and a low level does not exclude mesothelioma.
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| 27. |
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| 28. |
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| 29. |
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Internmedicin
- 2006
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Editorial collection (other academic/artistic)abstract
- Internmedicin är en heltäckande lärobok i ämnet och beskriver organrelaterade sjukdomar, allergier, förgiftningar och drogskador. Boken innehåller även ett kapitel i symtomlära. Sjukdomarna beskrivs grundligt med uppgifter om bland annat symtom, förekomst, etiologi, anamnes och utredning samt handläggning
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| 30. |
- Josefsson, Andreas, et al.
(author)
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Prostate cancer increases hyaluronan in surrounding nonmalignant stroma, and this response is associated with tumor growth and an unfavorable outcome
- 2011
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In: American Journal of Pathology. - : Elsevier BV. - 0002-9440 .- 1525-2191. ; 179:4, s. 1961-1968
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Journal article (peer-reviewed)abstract
- 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.
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| 31. |
- Kerje, Susanne, et al.
(author)
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Is low molecular hyaluronan an early indicator of disease in avian systemic sclerosis?
- 2016
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In: Connective Tissue Research. - : Taylor & Francis. - 0300-8207 .- 1607-8438. ; 57:5, s. 337-346
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Journal article (peer-reviewed)abstract
- 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.
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| 32. |
- Lindqvist, Ulla, et al.
(author)
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Dermal Distribution of Hyaluronan in Psoriatic Arthritis : Coexistence of CD44, MMP3 and MMP9
- 2012
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In: Acta Dermato-Venereologica. - Uppsala : Medical Journals Sweden AB. - 0001-5555 .- 1651-2057. ; 92:4, s. 372-377
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Journal article (peer-reviewed)abstract
- 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.
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| 33. |
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Medicin
- 2011
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Editorial collection (other academic/artistic)
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| 34. |
- Nyberg, A., et al.
(author)
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Serum hyaluronan and aminoterminal propeptide of type III procollagen in primary biliary cirrhosis : relation to clinical symptoms, liver histopathology and outcome
- 1992
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In: Journal of Internal Medicine. - 0954-6820 .- 1365-2796. ; 231:5, s. 485-491
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Journal article (peer-reviewed)abstract
- Hyaluronan (HA) and aminoterminal propeptide of type III procollagen (PIIINP), two biochemical connective tissue markers, were determined in 76 patients with primary biliary cirrhosis (PBC). The HA and PIIINP concentrations were significantly increased compared with controls (P less than 0.001). Both HA and PIIINP levels correlated significantly with conventional liver-function tests. All patients with stage IV PBC showed increased concentrations of both these variables. However, HA was a better marker with regard to prediction of development of cirrhosis as well as prediction of symptoms. Furthermore, HA also showed a negative correlation with time of survival (P less than 0.05). The present data indicate that HA is a more sensitive marker of liver damage in PBC than PIIINP.
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| 35. |
- Sundström, Gunnel, et al.
(author)
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Bone marrow hyaluronan and reticulin in patients with malignant disorders
- 2010
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In: Medical Oncology. - : Springer Science and Business Media LLC. - 1357-0560 .- 1559-131X. ; 27:3, s. 618-623
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Journal article (peer-reviewed)abstract
- 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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| 36. |
- Sundström, Gunnel, et al.
(author)
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Bone marrow hyaluronan distribution in patients with acute myeloid leukemia.
- 2005
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In: Medical Oncology. - 1357-0560 .- 1559-131X. ; 22:1, s. 71-78
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Journal article (peer-reviewed)abstract
- 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.
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| 37. |
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| 38. |
- Sundström, Gunnel, 1940-
(author)
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Hyaluronan in normal and malignant bone marrow : a clinical and morphological study with emphasis on myelofibrosis
- 2005
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Doctoral thesis (other academic/artistic)abstract
- Fibrosis in the bone marrow is usually denominated myelofibrosis and may contribute to impaired hematopoiesis. Myelofibrosis is seen both in malignant and non-malignant diseases. The normal microenvironment in the bone marrow consists of a heterogenous population of hematopoietic and non-hematopoietic stromal cells, their extracellular products and hematopoietic cytokines. The stromal cells produce a complex array of molecules, among others collagens and glycosaminoglycans (GAGs) of which hyaluronan (HYA) is the most abundant. Marrow fibrosis results from an increased deposition of collagens, which are polypeptides. Staining for reticulin, mostly composed of collagen type III, is the common way of visualizing myelofibrosis. HYA, like the collagens, is widely distributed in connective tissues. Little is known about the distribution of HYA in bone marrow. The aims of this thesis have been to determine how HYA is distributed in normal and malignant bone marrow, compared to reticulin staining, and to follow patients with chronic myeloproliferative diseases (CMPD) during two years treatment with anagrelide considering development of cellularity and fibrosis. In bone marrow biopsies from healthy volunteers, the controls, HYA was found in a pattern that was concordant with the reticulin staining. Comparing patients with different malignant diseases with and without bone marrow involvemen, HYA staining was found to be significantly stronger in both groups compared to the controls. The HYA scores were also significantly higher in the bone marrow of patients with de novo acute myeloid leukemia (AML), compared to the controls. There was a correlation between HYA and reticulin in the patients with de novo AML, and in the patients with different malignant diseases with and without bone marrow involvement as in the controls. Increase of HYA, reticulin and cellularity in the bone marrow of patients with CMPD after two years of treatment with anagrelide indicated progression of fibrosis. Anagrelide is a valuable drug for reduction of platelets but seems unable to stop progression of fibrosis and hypercellularity. HYA is an interesting molecule with properties not only contributing to the structure of extracellular matrix but also to cell signaling and behaviour, although the understanding of the detailed mechanisms is still incomplete.
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| 39. |
- Sundström, Gunnel, et al.
(author)
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Localisation and distribution of hyaluronan in normal bone marrow matrix : a novel method to evaluate impending fibrosis?
- 2002
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In: European Journal of Haematology. - : Wiley. - 0902-4441 .- 1600-0609. ; 68:4, s. 194-202
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Journal article (peer-reviewed)abstract
- Bone marrow trephine biopsies from 30 healthy volunteers, 10 men and 20 women aged 18-60 yr were obtained for identification and localisation of hyaluronan (HYA). Fixation, decalcification and embedding were performed by two different methods, with identical results in both. For comparison bone marrow trephine biopsies from three patients with different haematological diseases and known fibrosis were studied. All bone marrow specimens were also stained for reticulin grading. HYA was found in the bone marrow specimens from healthy individuals in a pattern that was concordant with the reticulin staining, the common way of visualising bone marrow fibrosis. In bone marrow from the patients with known fibrosis the HYA and reticulin staining were both more intense and abundant. Interestingly, HYA was also found intracellularly in eosinophilic cells in normal bone marrow. HYA is a polysaccharide unique both in structural and biological properties, and in excess it may predict bone marrow fibrosis.
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