1. |
- Lindblom, Per, 1974, et al.
(author)
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Endothelial PDGF-B retention is required for proper investment of pericytes in the microvessel wall.
- 2003
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In: Genes & development. - : Cold Spring Harbor Laboratory. - 0890-9369 .- 1549-5477. ; 17:15, s. 1835-40
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Journal article (peer-reviewed)abstract
- Several platelet-derived growth factor (PDGF) and vascular endothelial growth factor (VEGF) family members display C-terminal protein motifs that confer retention of the secreted factors within the pericellular space. To address the role of PDGF-B retention in vivo, we deleted the retention motif by gene targeting in mice. This resulted in defective investment of pericytes in the microvessel wall and delayed formation of the renal glomerulus mesangium. Long-term effects of lack of PDGF-B retention included severe retinal deterioration, glomerulosclerosis, and proteinuria. We conclude that retention of PDGF-B in microvessels is essential for proper recruitment and organization of pericytes and for renal and retinal function in adult mice.
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2. |
- 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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3. |
- Bondjers, Cecilia, 1974, et al.
(author)
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Transcription profiling of platelet-derived growth factor-B-deficient mouse embryos identifies RGS5 as a novel marker for pericytes and vascular smooth muscle cells.
- 2003
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In: The American journal of pathology. - 0002-9440. ; 162:3, s. 721-9
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Journal article (peer-reviewed)abstract
- All blood capillaries consist of endothelial tubes surrounded by mural cells referred to as pericytes. The origin, recruitment, and function of the pericytes is poorly understood, but the importance of these cells is underscored by the severe cardiovascular defects in mice genetically devoid of factors regulating pericyte recruitment to embryonic vessels, and by the association between pericyte loss and microangiopathy in diabetes mellitus. A general problem in the study of pericytes is the shortage of markers for these cells. To identify new markers for pericytes, we have taken advantage of the platelet-derived growth factor (PDGF)-B knockout mouse model, in which developing blood vessels in the central nervous system are almost completely devoid of pericytes. Using cDNA microarrays, we analyzed the gene expression in PDGF-B null embryos in comparison with corresponding wild-type embryos and searched for down-regulated genes. The most down-regulated gene present on our microarray was RGS5, a member of the RGS family of GTPase-activating proteins for G proteins. In situ hybridization identified RGS5 expression in brain pericytes, and in pericytes and vascular smooth muscle cells in certain other, but not all, locations. Absence of RGS5 expression in PDGF-B and PDGFR beta-null embryos correlated with pericyte loss in these mice. Residual RGS5 expression in rare pericytes suggested that RGS5 is a pericyte marker expressed independently of PDGF-B/R beta signaling. With RGS5 as a proof-of-principle, our data demonstrate the usefulness of microarray analysis of mouse models for abnormal pericyte development in the identification of new pericyte-specific markers.
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4. |
- Emgård, Per, et al.
(author)
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A topical steroid without an antibiotic cures external otitis efficiently : a study in an animal model.
- 2001
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In: European Archives of Oto-Rhino-Laryngology. - : Springer Science and Business Media LLC. - 0937-4477 .- 1434-4726. ; 258:6, s. 287-291
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Journal article (peer-reviewed)abstract
- In an animal external otitis model, inflammatory reactions were evoked by mechanical stimulation of the rat ear canal skin. The rats were in four groups: group A treated with a group III steroid, betamethasone dipropionate; group B treated with hydrocortisone combined with oxytetracycline; group C treated with hydrocortisone with oxytetracycline and polymyxin B added; Group D, the controls, treated with saline. All rats were observed otomicroscopically daily during the first 7 days after treatment and then on days 10 and 20. A standardized scoring system was used to evaluate colour, swelling and effusion of the ear canal. Histological specimens were collected on days 3, 7, 10 and 20. The most rapid improvement in the ear canal status occurred in the animals treated with betamethasone dipropionate. The inflammatory reaction of the ear canal skin caused by mechanical stimulation was characterized by oedema of the stroma but few inflammatory cells were present. The surface of the epithelium towards the connective tissue layer was smooth in the group III-treated animals (group A) whereas other groups had irregularities of the basal membrane. From this study it is inferred that the group III steroid betamethasone dipropionate alone heals experimentally induced external otitis more rapidly than hydrocortisone with oxytetracycline, with or without polymyxin B. These findings should be considered in future clinical trials of external otitis.
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5. |
- Eriksson, Per Olof, et al.
(author)
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Acute otitis media develops in the rat after intranasal challenge of Streptococcus pneumoniae.
- 2003
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In: The Laryngoscope. - 0023-852X .- 1531-4995. ; 113:11, s. 2047-2051
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Journal article (peer-reviewed)abstract
- OBJECTIVES/HYPOTHESIS: The rat is a frequently used animal model for middle ear research. To date, acute otitis media (AOM) has been evoked after instillation of bacteria directly into the middle ear cavity or after traumatizing the tympanic membrane. The purpose of the study was to examine whether, with an intact tympanic membrane and middle ear cavity, intranasally deposited bacteria cause AOM and how tympanic membrane stimulation influences this procedure. STUDY DESIGN: In vivo, murine model. METHODS: In a rat model, Streptococcus pneumoniae, type 3, was intranasally inoculated for 5 consecutive days. The tympanic membrane was treated with saline or with compound 48/80 or was left untreated. The development of AOM was evaluated by otomicroscopy, light microscopy, and middle ear culture. RESULTS: Ninety percent of the ears developed AOM. However, when the tympanic membranes were treated with saline or compound 48/80, only 40% and 57%, respectively, developed AOM. In all, 23 of 40 ears developed AOM and 20 ears showed growth of bacteria. CONCLUSION: Repeated intranasal deposition of S. pneumoniae, type 3, causes AOM in the rat. The development of AOM can be influenced by tympanic membrane stimulation.
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6. |
- Eriksson, Per Olof, et al.
(author)
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Degranulation of mast cells provokes a massive inflammatory reaction in the tympanic membrane.
- 2001
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In: The Laryngoscope. - : Wiley. - 0023-852X .- 1531-4995. ; 111:7, s. 1264-1270
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Journal article (peer-reviewed)abstract
- OBJECTIVE: The pars flaccida is extremely rich in mast cells. On stimulation the mast cells release preformed and de novo synthesized inflammatory substances. The purpose of this study was to examine how these mast cell substances provoke inflammatory changes in the tympanic membrane. STUDY DESIGN: In vivo, murine model. METHODS: In a rat model, the mast cell secretagogue compound 48/80 was applied locally to the tympanic membrane on 4 consecutive days and the ensuing inflammatory changes were evaluated by otological, light, and electron microscopy 3, 6, 9, 12, 18, 24, 36, and 48 hours and 4, 6, and 8 days later. RESULTS: Degranulation of the mast cells occurred within 3 hours of applying compound 48/80. Release of the mast cell substances coincided with an inflammatory event characterized by a two-stage reaction: an edema stage, peaking 6 hours after application, followed by a massive invasion of inflammatory cells, peaking at 24 and 48 hours. Pars flaccida and pars tensa were both involved, pars flaccida showing the earliest changes. Pars tensa exhibited the same biphasic reaction as pars flaccida, but approximately 6 hours later. CONCLUSIONS: The mast cells of the pars flaccida have the capacity to elicit an intense inflammation of the tympanic membrane. The biphasic reaction pattern resembles that observed in experimental otitis media, suggesting involvement of the mast cells in this inflammatory condition of the middle ear.
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7. |
- Eriksson, Per Olof, 1968-
(author)
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Developing otitis media : experimental studies in particular regarding inflammatory changes in the tympanic membrane
- 2004
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Doctoral thesis (other academic/artistic)abstract
- Otitis media (OM), one of the commonest of childhood diseases, causes much suffering. OM exists in a variety of forms, two of which are acute otitis media (AOM) and otitis media with effusion (OME). The clinical courses of these conditions differ, AOM usually presenting with earache, fever and/or aural discharge, and the OME usually with hearing impairment. The tympanic membrane (TM) mirrors the events in the middle ear cavity, and pars flaccida (PF) is the initial site of inflammatory changes in the TM. PF is rich in mast cells (MCs), which by releasing various mediators, may trigger TM inflammation. The aims of the present studies were to investigate early inflammatory changes in the TM in rat models of OM; after mast cell degranulation, in response to AOM, and OME, after myringotomy in AOM and in normal ears. Furthermore, we developed a new rat AOM model, that excludes surgical trauma and resembles the natural route of infection in man. AOM and OME elicited the first inflammatory response in PF of the TM. The response to OME was discrete, but a slight increase in macrophages was found. During the first 48 hours of AOM, the inflammatory response was intense, following a bimodal pattern. This reaction is similar to that found after MC degranulation. In AOM, macrophages were the predominant cell in PF, while in pars tensa (PT), polymorphonuclear cells (mainly neutrophils) predominated. When myringotomy was performed in AOM ears, the healing time was shorter than that of myringotomy in normal ears. The highly inflamed lamina propria seemed to promote healing. During early AOM, as well as following myringotomy, fibrin extravasates into PF and PT. This fibrin deposition may be involved in regulating the inflammatory response. Repeated nasal challenge with the otitis media pathogen Streptococcus pneumoniae provoked AOM and concomitant TM stimulation reduced the number of AOM cases. This new rat AOM model has the advantage of avoiding trauma in the middle ear cavity, while eliciting an intense inflammatory response in the middle ear cavity (MEC).
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8. |
- Eriksson, Per Olof, et al.
(author)
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First forty-eight hours of developing otitis media : An experimental study
- 2003
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In: Annals of Otology, Rhinology and Laryngology. - 0003-4894 .- 1943-572X. ; 112:6, s. 558-566
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Journal article (peer-reviewed)abstract
- The early inflammatory changes in the tympanic membrane were explored in 2 rat models. Acute otitis media was induced by instillation of Streptococcus pneumoniae type 3 into the middle ear cavity, and otitis media with effusion was induced by blockage of the eustachian tube. Otomicroscopic examination was performed before the rats were painlessly sacrificed at 3, 6, 9, 12, 18, 24, or 48 hours after initiation of the otitis media conditions. The tympanic membrane was studied by light and electron microscopy. Both acute otitis media and otitis media with effusion caused early inflammatory changes of the tympanic membrane, and the pars flaccida was the portion that reacted first. The inflammatory alterations were most pronounced in the acute otitis media model. The course of inflammation showed a bimodal pattern with an early deposition of a filamentous material with a band pattern, typical of fibrin. Despite a fluid-filled middle ear cavity, the inflammatory changes in the otitis media with effusion model were moderate, as was consistent with the clinical appearance of the tympanic membrane.
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9. |
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10. |
- Hellström, Anders, et al.
(author)
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Stereotyper i vardagen: Bilder av "de främmande"
- 2004
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In: Kategorisering och integration: om föreställda identiteter i politik, forskning, media och vardag, rapport från Integrationspolitiska maktutredningen / SOU 2004:48. - 0375-250X. - 9138221349 ; SOU 2004:48, s. 99-141
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Book chapter (other academic/artistic)
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