| 1. |
- Elgbratt, Kristina, 1969, et al.
(författare)
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Aberrant T-cell ontogeny and defective thymocyte and colonic T-cell chemotactic migration in colitis-prone Galphai2-deficient mice
- 2007
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Ingår i: Immunology. - : Wiley. - 0019-2805 .- 1365-2567. ; 122:2, s. 199-209
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Tidskriftsartikel (refereegranskat)abstract
- Galphai2-deficient mice, which spontaneously develop colitis, have previously been reported to have an increased frequency of mature, single positive thymocytes compared to wild-type mice. In this study we further characterized the intrathymic changes in these mice before and during overt colitis. Even before the onset of colitis, Galphai2(-/-) thymi weighed less and contained fewer thymocytes, and this was exacerbated with colitis development. Whereas precolitic Galphai2(-/-) mice had unchanged thymocyte density compared to Galphai2(+/-) mice of the same age, this was significantly decreased in mice with colitis. Thymic atrophy in Galphai2(-/-) mice involved mainly the cortex. Using a five-stage phenotypic characterization of thymocyte maturation based on expression of CD4, CD8, TCRalphabeta, CD69 and CD62L, we found that both precolitic and colitic Galphai2(-/-) mice had significantly increased frequencies of mature single-positive CD4(+) and CD8(+) medullary thymocytes, and significantly reduced frequencies and total numbers of immature CD4(+) CD8(+) double-positive thymocytes compared to Galphai2(+/-) mice. Furthermore, cortical and transitional precolitic Galphai2(-/-) thymocytes showed significantly reduced chemotactic migration towards CXCL12, and a trend towards reduced migration to CCL25, compared to wild-type thymocytes, a feature even more pronounced in colitic mice. This impaired chemotactic migration of Galphai2(-/-) thymocytes could not be reversed by increased chemokine concentrations. Galphai2(-/-) thymocytes also showed reduced expression of the CCL25 receptor CCR9, but not CXCR4, the receptor, for CXCL12. Finally, wild-type colonic lamina propria lymphocytes migrated in response to CXCL12, but not CCL25 and, as with thymocytes, the chemokine responsiveness was significantly reduced in Galphai2(-/-) mucosal lymphocytes.
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| 2. |
- Willén, Roger, 1939, et al.
(författare)
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Prophylactic surgery for patients with longstanding ulcerative colitis. Which option? Histopathological and clinical implications.
- 2007
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Ingår i: Upsala journal of medical sciences. - 2000-1967 .- 0300-9734. ; 112:1, s. 49-60
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Tidskriftsartikel (refereegranskat)abstract
- Patients with longstanding chronic ulcerative proctocolitis are at risk to develop colorectal cancer Conflicting views as regards surveillance, the indications for surgery and type of preventive procedure exist. For permanent prevention of cancer development complete removal of all potential malignant colorectal mucosa has to be done. Panprocto-colectomy with a conventional ileostomy or continent ileostomy removing all colorectal mucosa should therefore eliminate further risks of colorectal cancer. Colectomy and ileorectal anastomosis is a controversial issue. While many surgeons today are reluctant to use the technique, emphasising the persistent cancer risk, others consider the operation a viable alternative when used on a selective basis. The long-term risk of cancer in the rectal stump is the main strong argument . In restorative proctocolectomy, i.e. proctocolectomy with construction of an ileopouch anal anastomosis residual rectal mucosa is left behind irrespective of technique used and is therefore at risk for cancer development. Quite a few cancers have been reported to occur in these patients but controversy exists as regards the origin of these tumours but the risk for cancer development is very low. Biopsies from ileal pouches demonstrate various histopathological changes from nearly normal mucosa, to inflammation and atrophy, inflammatory cell changes, dysplasia as well as development of carcinoma. Grading of type and atypia is a challenge to reproduce and requires the participation of experienced gastrointestinal histopathologists.
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