| 1. |
- Aspholm-Hurtig, Marina, et al.
(författare)
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Functional adaptation of BabA, the H. pylori ABO blood group antigen binding adhesin.
- 2004
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Ingår i: Science (New York, N.Y.). - : American Association for the Advancement of Science (AAAS). - 1095-9203 .- 0036-8075. ; 305:5683, s. 519-22
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Tidskriftsartikel (refereegranskat)abstract
- Adherence by Helicobacter pylori increases the risk of gastric disease. Here, we report that more than 95% of strains that bind fucosylated blood group antigen bind A, B, and O antigens (generalists), whereas 60% of adherent South American Amerindian strains bind blood group O antigens best (specialists). This specialization coincides with the unique predominance of blood group O in these Amerindians. Strains differed about 1500-fold in binding affinities, and diversifying selection was evident in babA sequences. We propose that cycles of selection for increased and decreased bacterial adherence contribute to babA diversity and that these cycles have led to gradual replacement of generalist binding by specialist binding in blood group O-dominant human populations.
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| 2. |
- Caramori, G, et al.
(författare)
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Mucin expression in peripheral airways of patients with chronic obstructive pulmonary disease
- 2004
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Ingår i: Histopathology. - : Wiley. - 0309-0167 .- 1365-2559. ; 45:5, s. 477-484
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Tidskriftsartikel (refereegranskat)abstract
- Aims: To study the expression of mucins in peripheral airways in patients with chronic obstructive pulmonary disease (COPD). Methods and results: Peripheral lung sections from smokers with COPD (n = 9) and age-matched controls including smokers (n = 11) and lifelong non-smokers with normal lung function (n = 6) were stained with alcian blue, periodic acid-Schiff (PAS) and by immunohistochemistry of mucins (MUC): MUC2, MUC4, MUC5AC, MUC5B and MUC6. Histochemical staining and immunoreactivity of bronchiolar epithelium were graded and the presence or absence of stained mucus in the bronchiolar lumen was evaluated. There were no differences in alcian blue and PAS epithelial staining between the three groups. Intraluminal PAS staining was significantly more frequent among COPD subjects (P < 0.05). The expression of MUC5AC was significantly higher in the bronchiolar epithelium of patients with COPD (P < 0.05). Within the bronchiolar lumen, the predominant mucin was MUC5B. Intraluminal MUC5B was significantly more frequent among COPD patients (P < 0.05). Conclusions: COPD is specifically associated with increased expression of MUC5B in the bronchiolar lumen and of the mucin MUC5AC in the bronchiolar epithelium. These changes in mucin production in the peripheral airways may contribute to the pathophysiology of COPD.
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| 3. |
- Davies, Julia, et al.
(författare)
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Respiratory tract mucins : structure and expression patterns
- 2002
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Ingår i: Novartis Foundation symposium. - Chichester, UK : John Wiley & Sons, Ltd. - 1528-2511 .- 1935-4657. ; 248, s. 76-93
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Goblet cells produce mainly MUC5AC, but also MUC5B and some MUC2 in apparently ‘irritated’ airways. MUC5B dominates in the submucosal glands although a little MUC5AC and MUC7 are usually present. MUC4 originates from the ciliated cells. After separation into a gel and a sol phase, lysozyme and lactoferrin are enriched in the salivary gel phase suggesting that mucus may act as a matrix for ‘protective’ proteins on the mucosal surface. A salivary MUC5B N-terminal fragment consistent with a cleavage event in the D’ domain was de-tected with antibodies against various N-terminal peptide sequences suggesting that assembly of MUC5B occurs through a mechanism similar to that of the von Willebrand factor. Identification of additional cleavage sites C-terminal to the D’ domain suggests that most of the N-terminal low-glycosylated part of MUC5B may be removed without affecting the oligomeric nature of the mucin. Possibly, the generation of mucins with different macromolecular properties through proteolytic ‘processing’ is one way of adapting the mucus polymer matrix to meet local physiological demands. Monomeric mucins that appear to turn over rapidly in the airway epithelium have been identified using radiolabelled mucin precursors. ‘Shedding’ of such mucins after microbe attachment may prevent colonization of epithelial surfaces.
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| 4. |
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| 5. |
- Groneberg, DA, et al.
(författare)
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Distribution of respiratory mucin proteins in human nasal mucosa
- 2003
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Ingår i: Laryngoscope. - 1531-4995. ; 113:3, s. 520-524
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Tidskriftsartikel (refereegranskat)abstract
- Objectives/Hypothesis: The upper respiratory tract is involved in many acute and chronic respiratory tract diseases that present with the symptom of mucus hypersecretion. Mucin genes that encode for the backbone of glycoproteins contribute to the viscoelastic property of airway mucus. We examined the cellular expression and distribution of two major respiratory mucus-forming glycoproteins, MUC5AC and MUC5B, in normal human nasal tissues. Methods: Immunohistochemical analysis using polyclonal antibodies against the mucins MUC5AC and MUC5B was performed in normal human nasal tissues. Results: An abundant staining of submucosal mucus gland and epithelial goblet cells for MUC5B was found. hnmunohistochemical analysis of MUC5AC showed staining of surface epithelium goblet cells, whereas there was no staining of glandular cells. Comparison of the expression to lower airways revealed a similar pattern of expression of both mucins. Conclusions: The data in the present study demonstrated the localization of the two major respiratory mucin proteins in human nasal mucosa with a similar distribution of expression of MUC5AC and MUC5B in normal upper and lower airways. Mucin protein expression parallels that of mucin messenger RNA expression.
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| 6. |
- Groneberg, DA, et al.
(författare)
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Expression of MUC5AC and MUC5B mucins in normal and cystic fibrosis lung
- 2002
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Ingår i: Respiratory Medicine. - : Elsevier BV. - 1532-3064 .- 0954-6111. ; 96:2, s. 81-86
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Tidskriftsartikel (refereegranskat)abstract
- Hypersecretion of airway mucus is a characteristic feature of chronic airway diseases like cystic fibrosis (CF) and leads via impairment of the muco-ciliary clearance and bacterial superinfection to respiratory failure. The major components of the mucus matrix forming family of mucins in the airways are MUC5AC and MUC5B. To investigate the expression of these glycoproteins in CF, immunohistochemistry was carried out on trachea, bronchi and peripheral lung obtained from CF patients and compared to normal lung tissues. MUC5AC immunohistochemistry demonstrated signals in goblet cells of the epithelial lining. Also, goblet cells inside glandular secretory ducts revealed MUC5AC-positive staining. In comparison to those from normal subjects, CF sections were characterized by inflammatory changes and goblet cell hyperplasia, resulting in increased numbers of MUC5AC-positive cells. Immunohistochemical staining for MUC5B showed abundant staining of submucosal glands and epithelial goblet cells. Inside the glands, the immunoreactivity was restricted to glandular mucous cells, MUC5AC and MUC5B are expressed in the same histological pattern in CF compared to normal tissues with an increase of MUC5AC-positive cells due to goblet cell hyper- and metaplasia. (C) 2001 Elsevier Science Ltd.
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| 7. |
- Groneberg, DA, et al.
(författare)
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Expression of respiratory mucins in fatal status asthmaticus and mild asthma
- 2002
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Ingår i: Histopathology. - : Wiley. - 0309-0167. ; 40:4, s. 367-373
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Tidskriftsartikel (refereegranskat)abstract
- Aims: The airways of patients with asthma are characterized by chronic inflammatory changes comprising mainly T-cells and eosinophils, and airway remodelling with goblet cell metaplasia and submucosal gland hyperplasia. Mucus hypersecretion is often a marked feature, particularly in status asthmaticus. The matrix of airway sputum consists of high molecular glycoproteins and mucins. In this study, the expression and distribution of the major gelforming mucins MUC5AC and MUC5B were studied in fatal status asthmaticus tissues and bronchial biopsies of mild asthmatic patients. The effect of inhaled corticosteroids on the expression of these mucins was also investigated. Methods and results: Polyclonal antibodies specific for MUC5AC and MUC5B, and a monoclonal antibody for MUC5B were used to stain lung tissues and airway mucosal biopsies obtained from patients who died of status asthmaticus (n = 5) and from mild asthmatics (n = 4), respectively. Immunohistochemistry for MUC5AC revealed abundant staining of goblet cells situated in the epithelial surface lining and glandular ducts of tissues from patients with fatal asthma. MUC5B immunoreactivity was restricted to mucous cells of submucosal glands and to epithelial cells. In mild asthmatics, large amounts of MUC5B, but not MUC5AC, positive extracellular mucus was found in the airway lumen as plugs. adjacent to the epithelial lining and in the necks of glandular secretory ducts of mild asthmatics. The distribution of MUC5AC and MUC5B in bronchial biopsies of mild asthmatics was similar before and after inhaled steroid treatment. Conclusions: The expression of MUC5AC and MUC5B shares a similar distribution to normal airways in different states of asthma. The distribution is not affected by topical corticosteroid therapy.
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| 8. |
- Herrmann, Annkatrin, et al.
(författare)
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A high-density putative monomeric mucin is the major [(35)S]labelled macromolecular product of human colorectal mucins in organ culture.
- 2003
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Ingår i: Biochimie. - 1638-6183. ; 85:3-4, s. 381-390
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Tidskriftsartikel (refereegranskat)abstract
- We have studied the biosynthesis of mucins in organ cultures of human colon using isopycnic density-gradient centrifugation following pulse labelling with [35S]sulphate and [3H]-D-glucosamine. A high-density [35S]sulphate labelled component, of larger size than MUC2 monomers, appeared in the tissue and also in the medium. It was not degraded by reduction, trypsin digestion, digestion with chondroitin ABC lyase or heparan sulphate III lyase, but was cleaved into smaller fragments following alkaline borohydride treatment and appears to be a monomeric, mucin-like molecule containing a protease-resistant domain with a larger hydrodynamic volume than MUC2 monomers. Although this macromolecule incorporated much more radiolabel than MUC2, it was not detected using chemical analysis and thus appears to be a component with a high metabolic turnover present in a very small amount. Most of the [3H]-D-glucosamine label was associated with low-density material that was well separated from MUC2, which was poorly labelled. Most of MUC2 was associated with the tissue as an ‘insoluble’ complex. The amount of MUC2 remained constant and its associated radiolabel increased only slightly with time. Analysis of the MUC2 subunits from the reduced ‘insoluble’ complex showed the typical reduction-insensitive oligomers and confirmed that the radiolabel was associated with this mucin. The large size of the [35S]-labelled putative monomeric mucin makes it difficult to separate it from reduced insoluble complex MUC2. As a result, many studies of intestinal mucin synthesis and secretion in the past have most likely been performed on ‘mixtures’ of this mucin and MUC2 and are thus not possible to interpret as the metabolic behaviour of oligomeric mucins.
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| 9. |
- Larsson, Gerry, et al.
(författare)
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A comprehensive system for leader evaluation and development
- 2003
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Ingår i: Leadership & Organization Development Journal. - : Emerald. - 0143-7739 .- 1472-5347. ; 24:1, s. 16-25
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Tidskriftsartikel (refereegranskat)abstract
- The aim was to describe the development of a theoretical model for leader evaluation and development, an instrument based on this model, and a strategy for large scale implementation in the Swedish armed forces. The model rests on an interactional person by situation paradigm. It emphasises “developmental leadership”, which is inspired by transformational and functionalistic leadership approaches. The developmental leadership questionnaire (DLQ) was operationalised from the model and refined through structural equation modelling. The model and the DLQ will be used for three purposes: yearly evaluation of all personnel in the Swedish armed forces; yearly planning dialogues between each employee and his or her nearest supervisor; and a tool for leadership training. The implementation strategy includes an initial course in developmental leadership for all colonels. This is followed by the selection and training of local trainers, who, in turn, initiate the comprehensive programme locally. The system should be fully implemented by 2005.
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| 10. |
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