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- Perissinotto, D, et al.
(author)
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Avian neural crest cell migration is diversely regulated by the two major hyaluronan-binding proteoglycans PG-M/versican and aggrecan
- 2000
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In: Development: For advances in developmental biology and stem cells. - 1477-9129. ; 127:13, s. 2823-2842
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Journal article (peer-reviewed)abstract
- It has been proposed that hyaluronan-binding proteoglycans play an important role as guiding cues during neural crest (NC) cell migration, but their precise function has not been elucidated. In this study, we examine the distribution, structure and putative role of the two major hyaluronan-binding proteoglycans, PG-M/versicans and aggrecan, during the course of avian NC development. PG-M/versicans V0 and V1 are shown to be the prevalent isoforms at initial and advanced phases of NC cell movement, whereas the V2 and V3 transcripts are first detected following gangliogenesis. During NC cell dispersion, mRNAs for PG-M/versicans V0/V1 are transcribed by tissues lining the NC migratory pathways, as well as by tissues delimiting nonpermissive areas. Immunohistochemistry confirm the deposition of the macromolecules in these regions and highlight regional differences in the density of these proteoglycans. PG-M/versicans assembled within the sclerotome rearrange from an initially uniform distribution to a preferentially caudal localization, both at the mRNA and protein level. This reorganization is a direct consequence of the metameric NC cell migration through the rostral portion of the somites. As suggested by previous in situ hybridizations, aggrecan shows a virtually opposite distribution to PG-M/versicans being confined to the perinotochordal ECM and extending dorsolaterally in a segmentally organized manner eventually to the entire spinal cord at axial levels interspacing the ganglia. PG-M/versicans purified from the NC migratory routes are highly polydispersed, have an apparent M(r) of 1,200-2,000 kDa, are primarily substituted with chondroitin-6-sulfates and, upon chondroitinase ABC digestion, are found to be composed of core proteins with apparent M(r )of 360-530, 000. TEM/rotary shadowing analysis of the isolated PG-M/versicans confirmed that they exhibit the characteristic bi-globular shape, have core proteins with sizes predicted for the V0/V1 isoforms and carry relatively few extended glycosaminoglycan chains. Orthotopical implantation of PG-M/versicans immobilized onto transplantable micromembranes tend to 'attract' moving cells toward them, whereas similar implantations of a notochordal type-aggrecan retain both single and cohorts of moving NC cells in close proximity of the implant and thereby perturb their spatiotemporal migratory pattern. NC cells fail to migrate through three-dimensional collagen type I-aggrecan substrata in vitro, but locomote in a haptotactic manner through collagen type I-PG-M/versican V0 substrata via engagement of HNK-1 antigen-bearing cell surface components. The present data suggest that PG-M/versicans and notochordal aggrecan exert divergent guiding functions during NC cell dispersion, which are mediated by both their core proteins and glycosaminoglycan side chains and may involve 'haptotactic-like' motility phenomena. Whereas aggrecan defines strictly impenetrable embryonic areas, PG-M/versicans are central components of the NC migratory pathways favoring the directed movement of the cells.
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- Akerlund, JE, et al.
(author)
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Pouchitis
- 2004
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In: Current opinion in gastroenterology. - : Ovid Technologies (Wolters Kluwer Health). - 0267-1379. ; 20:4, s. 341-344
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Journal article (peer-reviewed)
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- Sjoqvist, U, et al.
(author)
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Chronic colitis is associated with a reduction of mucosal alkaline sphingomyelinase activity
- 2002
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In: Inflammatory Bowel Diseases. - : Oxford University Press (OUP). - 1536-4844 .- 1078-0998. ; 8:4, s. 258-263
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Journal article (peer-reviewed)abstract
- Background and Aims: The hydrolysis of sphingomyelin (SM) generates key molecules regulating cell growth. Animal cancer studies support an inhibitory role for this pathway in the malignant transformation of the colonic mucosa. The activity of a specific intestinal alkaline sphingomyelinase (SMase), which hydrolyzes SM, is reduced in colorectal tumors. In this study we measured alkaline SMase activity in patients with longstanding colitis and assessed if a reduction can be used as a marker in surveillance of high risk patients. Methods: Alkaline SMase activity was measured in 139 colonic biopsies from 34 patients with longstanding, extensive colitis and from I I controls. Fifteen patients had earlier diagnosis of dysplasia or DNA aneuploidy. Alkaline SMase activity was related to histologic dysplasia and DNA aneuploidy assessed by flow cytometry, patient age, and duration of disease. Results: Alkaline SMase activity was significantly lower in the patient group with and without dysplasia compared with controls (p = 0.006). In biopsies, an association was not found between alkaline SMase activity, dysplasia, or DNA ploidy. However, alkaline SMase activity decreased with age both in patients and controls (p = 0.008). Conclusions: Reduction of alkaline SMase activity seen in colorectal cancer and adenomas is also present in patients with chronic colitis. It is not complementary to dysplasia or DNA-aneuploidy in the identification of high risk patients. The age-associated decrease of alkaline SMase activity seems to be a general phenomenon indicating premature senescence of the mucosa in longstanding colitis.
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- Torkvist, L, et al.
(author)
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Heparin protects against skin flap necrosis: relationship to neutrophil recruitment and anti-coagulant activity
- 2004
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In: Inflammation Research. - : Springer Science and Business Media LLC. - 1420-908X .- 1023-3830. ; 53:1, s. 1-3
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Journal article (peer-reviewed)abstract
- Objective and design: Heparin has been shown to improve survival of surgical skin flaps. However, it is not known whether the protective effect of heparin is related to it's anticoagulative or anti-inflammatory effects. Methods: Surgical flaps were raised in the dorsal skin of Sprague-Dawley rats. Neutrophil recruitment was determined by measuring the tissue content of myeloperoxidase (MPO) and clotting time was estimated by assessment of activated partial thromboplastin time (APTT) in plasma. Results: Administration of heparin (150 U/kg) significantly increased skin flap survival from 44 % in vehicle-treated controls to 91 %. This heparin treatment increased APTT by 4.5 fold. However, administration of 150 U/kg of heparin had no effect on skin flap neutrophil recruitment. In contrast, we found that the polysaccharide fucoidan reduced MPO and also improved skin flap survival. Conclusions: In conclusion, we demonstrate that protective effect of clinically relevant doses of heparin correlates with its' ability to prolong clotting time and not to inhibition of neutrophil accumulation in the healing of skin flaps.
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