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- Falconer, C, et al.
(författare)
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Different organization of collagen fibrils in stress-incontinent women of fertile age
- 1998
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Ingår i: Acta Obstetricia et Gynecologica Scandinavica. - 0001-6349. ; 77, s. 87-
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: The objective was to test the hypothesis that stress urinary incontinence in women is correlated to changes in the paraurethral connective tissue ultrastructure and metabolism.METHODS: Transvaginal biopsies were obtained from the paraurethral connective tissue in women of fertile age with stress urinary incontinence and in matched continent controls. All the stress-incontinent women were characterized with urodynamic investigation. In the biopsies, collagen concentration, measured as hydroxyproline, and the degree of extraction by pepsin digestion were quantified. Proteoglycan composition and concentration were analyzed using Alcian blue precipitation, followed by electrophoretic separation and quantification. Using Northern blots mRNA levels for the collagens I and III, the small proteoglycans decorin and biglycan, and the large proteoglycan versican, were quantified. Collagen organization was examined with transmission electron microscopy and the diameters of collagen fibrils were analyzed with an interactive image analysis system (IBAS, Zeiss/Kontron).RESULTS: The biochemical and morphological analyses exposed a significant difference in the paraurethral connective tissue between stress urinary incontinent women before menopause and comparable controls. The collagen concentration was almost 30% higher and the diameters of the collagen fibrils were 30% larger in the incontinent group of women. Also the organization of the collagen fibrils differed, with considerably higher cross-linking. A higher level of mRNA for collagen I and III in the incontinent group indicates that the differences can be related to an altered collagen metabolism. No change of proteoglycan amount or composition was observed, resulting in a significantly lower proteoglycan/collagen ratio in the incontinent group of women.CONCLUSION: Stress urinary incontinence in fertile women is associated with a change in collagen metabolism resulting in an increased concentration of collagen and larger collagen fibrils. These alterations should result in a more rigid form of extracellular matrix, suggesting a connective tissue with impaired mechanical function.
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| 2. |
- Westergren-Thorsson, Gunilla, et al.
(författare)
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Differential expressions of mRNA for proteoglycans, collagens and transforming growth factor-beta in the human cervix during pregnancy and involution
- 1998
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Ingår i: Biochimica et Biophysica Acta. - 0006-3002. ; 1406:2, s. 13-203
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Tidskriftsartikel (refereegranskat)abstract
- During pregnancy and involution, an extensive remodelling of the human cervical connective tissue occurs. This cervical ripening is one of the most pronounced physiological remodelling processes known in human connective tissue. To investigate how the remodelling is accomplished, the levels of mRNA for collagen I and III, versican and three small proteoglycans, biglycan, decorin and fibromodulin, were evaluated using Northern blots at different stages of cervical ripening. In the corresponding biopsies the concentration of collagen and of small and large proteoglycans were determined. The role of transforming growth factor-beta (TGF-beta) as a mediator of the remodelling process was also investigated. The concentration of collagen decreased and 1 week before partus, 50% of the nonpregnant level was attained. No further decrease was noted after partus. The mRNA for collagen I and III did, however, not decrease in the term pregnant cervix 1 week before partus. Only 20-30% decrease during the final ripening just before partus was recorded. Neither did the mRNA levels of the small proteoglycans change significantly during the ripening, despite an almost 50% decrease in the concentration of the small proteoglycans. The message for versican was, however, 5-fold increased at partus and then gradually returned to nonpregnant levels within 4 days after delivery. These changes corresponded to similar changes in the concentration of the large proteoglycan. Thus, the remodelling of the cervical connective tissue is achieved by two different mechanisms, on one hand an increased turnover of collagen and the small proteoglycans, on the other a changed transcription followed by an increased production of versican. During the involution 2- to 3-fold increases in the messages for collagen I and III, and the small proteoglycans, biglycan and decorin, corresponded to increases in the concentration of the small proteoglycans and non-extractable collagen. The message for TGF-beta was increased 2-fold immediately after delivery compared with the term pregnant state. Thus, TGF-beta may be of importance for the reconstruction of the cervix, which starts immediately after partus.
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