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  • 1.
    Aabel, Peder
    et al.
    Oslo Univ Hosp, Dept Med Biochem, Oslo, Norway;Akershus Univ Hosp, Ear Nose & Throat Dept, Div Surg, Lorenskog, Norway;Univ Oslo, Inst Clin Med, Div Surg, Oslo, Norway.
    Utheim, Tor Paaske
    Oslo Univ Hosp, Dept Med Biochem, Oslo, Norway;Univ Oslo, Inst Oral Biol, Fac Dent, Oslo, Norway.
    Olstad, Ole Kristoffer
    Oslo Univ Hosp, Dept Med Biochem, Oslo, Norway.
    Rask-Andersen, Helge
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Dilley, Rodney James
    Ear Sci Inst Australia, Perth, WA, Australia;Univ Western Australia, Ear Sci Ctr, Nedlands, WA, Australia;Univ Western Australia, Ctr Cell Therapy & Regenerat Med, Nedlands, WA, Australia.
    von Unge, Magnus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland. Akershus Univ Hosp, Ear Nose & Throat Dept, Div Surg, Lorenskog, Norway;Univ Oslo, Inst Clin Med, Div Surg, Oslo, Norway.
    Transcription and microRNA Profiling of Cultured Human Tympanic Membrane Epidermal Keratinocytes2018In: Journal of the Association for Research in Otolaryngology, ISSN 1525-3961, E-ISSN 1438-7573, Vol. 19, no 3, p. 243-260Article in journal (Refereed)
    Abstract [en]

    The human tympanic membrane (TM) has a thin outer epidermal layer which plays an important role in TM homeostasis and ear health. The specialised cells of the TM epidermis have a different physiology compared to normal skin epidermal keratinocytes, displaying a dynamic and constitutive migration that maintains a clear TM surface and assists in regeneration. Here, we characterise and compare molecular phenotypes in keratinocyte cultures from TM and normal skin. TM keratinocytes were isolated by enzymatic digestion and cultured in vitro. We compared global mRNA and microRNA expression of the cultured cells with that of human epidermal keratinocyte cultures. Genes with either relatively higher or lower expression were analysed further using the biostatistical tools g:Profiler and Ingenuity Pathway Analysis. Approximately 500 genes were found differentially expressed. Gene ontology enrichment and Ingenuity analyses identified cellular migration and closely related biological processes to be the most significant functions of the genes highly expressed in the TM keratinocytes. The genes of low expression showed a marked difference in homeobox (HOX) genes of clusters A and C, giving the TM keratinocytes a strikingly low HOX gene expression profile. An in vitro scratch wound assay showed a more individualised cell movement in cells from the tympanic membrane than normal epidermal keratinocytes. We identified 10 microRNAs with differential expression, several of which can also be linked to regulation of cell migration and expression of HOX genes. Our data provides clues to understanding the specific physiological properties of TM keratinocytes, including candidate genes for constitutive migration, and may thus help focus further research.

  • 2.
    Fransen, Erik
    et al.
    University of Antwerp, Belgium .
    Topsakal, Vedat
    University Hospital of Antwerp, Belgium .
    Hendrickx, Jan-Jaap
    Van Laer, Lut
    University of Antwerp, Belgium .
    Huyghe, Jeroen
    University of Antwerp, Belgium .
    Van Eyken, Els
    University of Antwerp, Belgium .
    Lemkens, Nele
    University Hospital of Antwerp, Belgium .
    Hannula, Samuli
    University of Oulu, Finland.
    Mäki-Torkko, Elina
    Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Reconstruction Centre, Department of ENT - Head and Neck Surgery UHL. University of Oulu, Finland .
    Jensen, Mona
    Bispebjerg Hospital, Copenhagen, Denmark .
    Demeester, Kelly
    University Hospital of Antwerp, Belgium .
    Tropitzsch, Anke
    University of Tuebingen, Germany .
    Bonaconsa, Amanda
    University Hospital Padova, Italy.
    Mazzoli, Manuela
    University Hospital Padova, Italy.
    Espeso, Angeles
    Cardiff University, UK .
    Verbruggen, Katia
    University Hospital of Gent, Belgium .
    Huyghe, Joke
    University Hospital of Gent, Belgium .
    Huygen, Patrick
    Radboud University Nijmegen Medical Centre, The Netherlands .
    Kunst, Sylvia
    Radboud University Nijmegen Medical Centre, The Netherlands .
    Manninen, Minna
    University of Tampere, Finland.
    Diaz-Lacava, Amalia
    University of Bonn, Germany.
    Steffens, Michael
    University of Bonn, Germany.
    Wienker, Thomas
    University of Bonn, Germany.
    Pyykkö, Ilmari
    University of Tampere, Finland.
    Cremers, Cor
    Radboud University Nijmegen Medical Centre, The Netherlands .
    Kremer, Hannie
    Radboud University Nijmegen Medical Centre, The Netherlands .
    Dhooge, Ingeborg
    University Hospital of Gent, Belgium.
    Stephens, Dafydd
    Cardiff University, UK.
    Orzan, Eva
    University Hospital Padova, Italy.
    Pfister, Markus
    University of Tuebingen, Germany.
    Bille, Mikael
    Bispebjerg Hospital, Copenhagen, Denmark.
    Parving, Agnete
    Bispebjerg Hospital, Copenhagen, Denmark.
    Sorri, Martti
    University of Oulu, Finland.
    Van de Heyning, Paul
    University Hospital of Antwerp, Belgium.
    Van Camp, Guy
    University of Antwerp, Belgium.
    Occupational Noise, Smoking, and a High Body Mass Index are Risk Factors for Age-related Hearing Impairment and Moderate Alcohol Consumption is Protective: A European Population-based Multicenter Study2008In: Journal of the Association for Research in Otolaryngology, ISSN 1525-3961, E-ISSN 1438-7573, Vol. 9, no 3, p. 264-276Article in journal (Refereed)
    Abstract [en]

    A multicenter study was set up to elucidate the environmental and medical risk factors contributing to age-related hearing impairment (ARHI). Nine subsamples, collected by nine audiological centers across Europe, added up to a total of 4,083 subjects between 53 and 67 years. Audiometric data (pure-tone average [PTA]) were collected and the participants filled out a questionnaire on environmental risk factors and medical history. People with a history of disease that could affect hearing were excluded. PTAs were adjusted for age and sex and tested for association with exposure to risk factors. Noise exposure was associated with a significant loss of hearing at high sound frequencies (>1 kHz). Smoking significantly increased high-frequency hearing loss, and the effect was dose-dependent. The effect of smoking remained significant when accounting for cardiovascular disease events. Taller people had better hearing on average with a more pronounced effect at low sound frequencies (<2 kHz). A high body mass index (BMI) correlated with hearing loss across the frequency range tested. Moderate alcohol consumption was inversely correlated with hearing loss. Significant associations were found in the high

  • 3.
    Hultgård-Ekwall, Anna-Karin
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Mayerl, Christina
    Rubin, Kristofer
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Wick, Georg
    Rask-Andersen, Helge
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    An interstitial network of podoplanin-expressing cells in the human endolymphatic duct2006In: Journal of the Association for Research in Otolaryngology, ISSN 1525-3961, E-ISSN 1438-7573, Vol. 7, no 1, p. 38-47Article in journal (Refereed)
    Abstract [en]

    The human endolymphatic duct (ED) with encompassing interstitial connective tissue (CT) is believed to be important for endolymph resorption and fluid pressure regulation of the inner ear. The periductal CT cells are interconnected via numerous cellular extensions, but do not form vessel structures. Here we report that the periductal CT is populated by two distinct cell phenotypes; one expressing podoplanin, a protein otherwise found on lymph endothelia and on epithelia involved in fluid fluxes, and a second expressing a fibroblast marker. A majority of the interstitial cells expressed podoplanin but not the lymphatic endothelial cell markers hyaluronan receptor (LYVE-1) or vascular endothelial growth factor receptor-3 (VEGFR-3). The fibroblast marker positive cells were found close to the ED epithelium. In the mid- and distal parts of the ED, these cells were enriched under folded epithelia. Furthermore, subepithelial CT cells were found to express activated platelet derived growth factor (PDGF)-beta receptors. Cultured CT cells from human inner ear periductal and perisaccular explant tissues were identified as fibroblasts. These cells compacted a three-dimensional collagen lattice by a process that could be promoted by PDGF-BB, a factor involved in interstitial fluid pressure regulation. Our results are compatible with the notion that the periductal CT cells are involved in the regulation of inner ear fluid pressure. By active compaction of the periductal CT and by the formation of villous structures, the CT cells could modulate fluid fluxes over the ED epithelium as well as the longitudinal flow of endolymph in the ED.

  • 4.
    Santi, Peter A.
    et al.
    Univ Minnesota, Dept Otolaryngol, Lions Res Bldg 2001 Sixth St,SE, Minneapolis, MN 55455 USA..
    Aldaya, Robair
    Univ Minnesota, Dept Otolaryngol, Lions Res Bldg 2001 Sixth St,SE, Minneapolis, MN 55455 USA..
    Brown, Alec
    Univ Minnesota, Dept Otolaryngol, Lions Res Bldg 2001 Sixth St,SE, Minneapolis, MN 55455 USA..
    Johnson, Shane
    Univ Minnesota, Dept Otolaryngol, Lions Res Bldg 2001 Sixth St,SE, Minneapolis, MN 55455 USA..
    Stromback, Tyler
    Univ Minnesota, Dept Otolaryngol, Lions Res Bldg 2001 Sixth St,SE, Minneapolis, MN 55455 USA..
    Cureoglu, Sebahattin
    Univ Minnesota, Dept Otolaryngol, Lions Res Bldg 2001 Sixth St,SE, Minneapolis, MN 55455 USA..
    Rask-Andersen, Helge
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Scanning Electron Microscopic Examination of the Extracellular Matrix in the Decellularized Mouse and Human Cochlea2016In: Journal of the Association for Research in Otolaryngology, ISSN 1525-3961, E-ISSN 1438-7573, Vol. 17, no 3, p. 159-171Article in journal (Refereed)
    Abstract [en]

    Decellularized tissues have been used to investigate the extracellular matrix (ECM) in a number of different tissues and species. Santi and Johnson JARO 14: 3-15 (2013) first described the decellularized inner ear in the mouse, rat, and human using scanning thin-sheet laser imaging microscopy (sTSLIM). The purpose of the present investigation is to examine decellularized cochleas in the mouse and human at higher resolution using scanning electron microscopy (SEM). Fresh cochleas were harvested and decellularized using detergent extraction methods. Following decellularization, the ECM of the bone, basilar membrane, spiral limbus, and ligament remained, and all of the cells were removed from the cochlea. A number of similarities and differences in the ECM of the mouse and human were observed. A novel, spirally directed structure was present on the basilar membrane and is located at the border between Hensen and Boettcher cells. These septa-like structures formed a single row in the mouse and multiple rows in the human. The basal lamina of the stria vascularis capillaries was present and appeared thicker in the human compared with the mouse. In the mouse, numerous openings beneath the spiral prominence that previously housed the root processes of the external sulcus cells were observed but in the human there was only a single row of openings. These and other anatomical differences in the ECM between the mouse and human may reflect functional differences and/or be due to aging; however, decellularized cochleas provide a new way to examine the cochlear ECM and reveal new observations.

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