| 11. |
- Nilsson, Ingrid, et al.
(författare)
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Helicobacter ganmani infection associated with a spontaneous outbreak of inflammatory bowel-like disease in an IL-10-deficient mouse colony
- 2008
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Ingår i: Scandinavian Journal of Laboratory Animal Science. - 0901-3393. ; 35:1, s. 13-24
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Tidskriftsartikel (refereegranskat)abstract
- Background: A breeding colony of IL-10 deficient B6.129P2-Il10(tmICgn/J) mice, kept under conventional conditions, developed an inflammatory bowel-like disease (IBD) with rectal prolapse and blood tinged diarrhoea. No clinical signs of disease were observed at the time of arrival to our animal house. These animals were originally planned to serve as a negative control group in an experimental infection study with Helicobacter species to investigate colonization of the murine gut. Results: A spiral-shaped, Gram-negative bacterium was isolated from the breeding mice colony. In a first group of six animals, tissue specimens from the liver, small and large intestines, faeces and blood, were analysed by culture, PCR-denaturing gradient gel electrophoresis (PCR-DGGE), species-specific PCR assays and DNA-sequencing, histology and serology. Helicobacter ganmani, but no other Helicobacter species, was isolated from the liver, small bowel, caecum, colon and faeces. We found inflammation in caeca, colon and livers, most pronounced in the caecal areas of culture positive mice with a severe typhlitis with cystic dilatation of glandular structures and irregular crypt architecture. Some animals showed a pronounced colitis with mucosal and sub-mucosal inflammatory infiltrates. Other animals displayed large lymphoid infiltrates in the livers and hepatitis. Tissue samples and sera from 18 additional animals from the same breeding colony were analysed by the same methods, except for culture. H. ganmani was identified by PCR in most tissue samples of the 18 additional animals as well. Sero-conversion to H. ganmani correlated well with histopathological changes. Conclusions: Our findings emphasize the importance of using Helicobacter-free animals to develop murine models of chronic hepatitis and colitis.
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| 12. |
- Odin, Elisabeth, 1955, et al.
(författare)
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Expression and clinical significance of methylenetetrahydrofolate reductase in patients with colorectal cancer
- 2006
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Ingår i: Clin Colorectal Cancer. - 1533-0028. ; 5:5, s. 344-9
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The aim of the study was to investigate the influence of methylenetetrahydrofolate reductase (MTHFR) gene expression levels and MTHFR polymorphism C677T on the outcome of patients with colorectal cancer (CRC). Furthermore, we wanted to evaluate the interaction between MTHFR and thymidylate synthase (TS) and folylpolyglutamate synthase (FPGS) and to investigate the impact of folate concentration on patients with CRC with different MTHFR genotypes. PATIENTS AND METHODS: The frequency of MTHFR polymorphism C677T was determined (n = 147), and gene expression levels of MTHFR, TS, and FPGS were quantified with real-time polymerase chain reaction (n = 157). Reduced folates in tissue were measured with a binding assay (n = 40). RESULTS: We observed a significantly lower concentration of tetrahydrofolate (THF) in patients with CT or TT genotypes compared with patients having the CC genotype. Twenty-six patients with Dukes A to C tumors who had not been subjected to chemotherapy relapsed. Out of these, 18 had CT or TT genotypes, and only 8 had the CC genotype (P = 0.045). Furthermore, 75 patients did not relapse, and out of these, 35 had CT or TT genotypes, and 40 had the CC genotype. The relative gene expression level of MTHFR in patients subgrouped by CC and CT or TT genotypes was significantly lower in carcinomas compared with adjacent mucosa (P < 0.0001 and P < 0.0001, respectively). A significant difference in MTHFR expression level was also observed according to MTHFR genotype in the tumor but not in adjacent mucosa. The MTHFR gene expression level in mucosa was a prognostic parameter independent of the clinicopathologic factors with regard to survival for patients with MTHFR C677T mutation. CONCLUSION: Our results showed that it is possible to identify patients with CRC with a higher risk for relapse. Furthermore, patients with a mutant genotype in combination with low MTHFR expression have a poor clinical outcome.
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| 13. |
- Solberg, Anna, 1961, et al.
(författare)
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Progress of tissue injury in appendicitis involves the serine proteases uPA and PAI-1.
- 2009
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Ingår i: Scandinavian journal of gastroenterology. - : Informa UK Limited. - 1502-7708 .- 0036-5521. ; 44:5, s. 579-84
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Serine proteases and the matrix metalloproteinases (MMPs) are key factors in the proteolytic cascade and participate in extracellular matrix (ECM) degradation. Fibrinolytic activators and inhibitors may have an effect on inflammatory cells, thereby modulating the inflammatory response. It is reasonable to assume that they may be implicated in the tissue injury in acute appendicitis that subsequently leads to appendix perforation. The purpose of this study was to investigate the expression and distribution of urokinase-type plasminogen activator (uPA) and plasminogen-activator inhibitor type 1 (PAI-1) in appendicitis. MATERIAL AND METHODS: Expression of uPA and expression of PAI-1 were measured in tissue specimens from patients with appendicitis (n=30) and in control specimens (n=9), using the quantitative ELISA technique. Distribution of enzymes was studied with immunohistochemistry. The uPA and PAI-1 levels in the subgroups of appendicitis and controls were compared. RESULTS: The overall expressions of uPA and PAI-1 were greater in appendicitis than in control specimens (p <0.001 and p<0.0001, respectively). Expressions of uPA and PAI-1 in phlegmonous (n=15), gangrenous (n=6) and perforated appendicitis (n=9) were all higher than those in controls (n=9), (p<0.01). Moreover, the PAI-1 level was elevated in perforated appendicitis compared with phlegmonous appendicitis (p<0.01). uPA staining was observed in connection with vascular endothelial cells and the serosa stained intensely in specimens from perforated appendicitis. CONCLUSIONS: The expression of uPA and especially the over-expression of PAI-1 seem to correlate to the progression of local inflammatory response in acute appendicitis.
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| 14. |
- Wettergren, Yvonne, 1957, et al.
(författare)
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Low expression of reduced folate carrier-1 and folylpolyglutamate synthase correlates with lack of a deleted in colorectal carcinoma mRNA splice variant in normal-appearing mucosa of colorectal carcinoma patients
- 2005
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Ingår i: Cancer Detect Prev. - : Elsevier BV. - 0361-090X .- 1525-1500. ; 29:4, s. 348-55
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Cellular folate deficiency leads to DNA strand breaks, mutations, and aberrant methylation and might be a risk factor for colorectal cancer (CRC). The putative tumor suppressor gene deleted in colorectal carcinoma (DCC) is one of several genes the expression of which seems to be affected by the folate concentration at the tissue level. Decreased expression of DCC may be caused by LOH or hypermethylation, i.e. by events that might be linked to folate deficiency. The purpose of this study was to analyze if the folate level and the gene expression levels of reduced folate carrier (RFC-1) and folylpolyglutamate synthase (FPGS) had impact on the expression of DCC splice variants. METHODS: Quantification of RFC-1 and FPGS expression in mucosa of 53 CRC patients was performed using real-time PCR whereas DCC splicing variants were detected by automated capillary gel electrophoresis. Total reduced folate concentration was measured with the FdUMP-binding assay (n = 22). RESULTS: Significantly higher expression levels of RFC-1 (p = 0.026) and FPGS (p = 0.05) were found in mucosa expressing the splice variant DCC342 compared to mucosa that did not. Furthermore, multivariate analysis showed that RFC-1 and FPGS (r = 0.49, p = 0.01) as well as folate and RFC-1 (r = 0.56, p = 0.023) were correlated only in mucosa expressing DCC342. CONCLUSIONS: In conclusion, the present study points to a potential influence of folates in regulating DCC expression at multiple levels involving post-transcriptional pathways. The results may provide a basis for a detailed investigation of molecular mechanisms involved in folate regulation of DCC expression.
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| 15. |
- 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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| 16. |
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