| 11. |
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| 12. |
- 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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| 13. |
- Nordengren, Johanna, et al.
(författare)
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High tumor tissue concentration of plasminogen activator inhibitor 2 (PAI-2) is an independent marker for shorter progression-free survival in patients with early stage endometrial cancer.
- 2002
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Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136. ; 97:3, s. 379-385
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Tidskriftsartikel (refereegranskat)abstract
- Previous studies including various tumor types have shown different associations between tumor tissue levels of plasminogen activator inhibitor 2 (PAI-2) and patient survival. High tumor tissue concentrations of PAI-2 have been associated with good prognosis in patients with breast cancer, small cell lung cancer and ovarian cancer, but with poor histologic differentiation and poor prognosis in patients with colorectal cancer. On the other hand, high tumor tissue concentrations of urokinase plasminogen activator (uPA), uPA receptor (R) and PAI-1 have more consistently been associated with poor histologic differentiation and poor prognosis. Our study quantified PAI-2 and uPAR using specific enzyme-linked immunosorbent assays in homogenates of 274 samples of endometrial cancer tissue. The prognostic power of each factor was analyzed in the subgroup of patients with early stage disease, i.e., International Federation of Gynecology and Oncology (FIGO) surgical stage I-II (n = 188). This group had a median follow-up time of 6.8 years (range 0.7-9.9), and 23 progressions were observed. The 80(th) percentile for PAI-2 and uPAR was used to dichotomize the material, and the results were analyzed for associations with clinical data including progression-free survival. The results were also compared with DNA ploidy status, S-phase fraction, uPA and PAI-1, which we reported in a previous study (Fredstorp Lidebring et al., Eur J Cancer 2001; in press). A high PAI-2 level was associated with shorter progression-free survival in univariate analysis and was an independent prognostic factor in bivariate analyses, which included PAI-1, uPA and DNA ploidy status. In contrast, a high level of uPAR had no association with prognosis in early stage endometrial cancer. The combination of high PAI-2 and PAI-1 levels in tumors revealed a small group of stage I-II patients with an accumulative progression rate of 50%.
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| 14. |
- Odin, Elisabeth, 1955, et al.
(författare)
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Altered gene expression of folate enzymes in adjacent mucosa is associated with outcome of colorectal cancer patients.
- 2003
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Ingår i: Clinical cancer research : an official journal of the American Association for Cancer Research. - 1078-0432 .- 1557-3265. ; 9:16 Pt 1, s. 6012-9
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: The purpose of this study was to analyze whether gene expression levels of folate enzymes in adjacent mucosa were associated with outcome of colorectal cancer patients. EXPERIMENTAL DESIGN: Real-time PCR was used to quantify expression levels of folate-associated genes including the reduced folate carrier (RFC-1), folylpolyglutamate synthase (FPGS), gamma-glutamyl hydrolase (GGH),and thymidylate synthase (TS) in tumor tissue and adjacent mucosa of patients with primary colorectal cancer (n=102). Furthermore, reduced folates in the tissues were measured with a binding-assay method. RESULTS: Mean gene expression levels of RFC-1, FPGS, GGH, and TS were significantly higher in tumor biopsies compared with mucosa. Univariate and multivariate analyses showed that the FPGS gene expression level in mucosa, but not in tumor, was a prognostic parameter independent of the clinicopathological factors with regard to survival. Patients with high FPGS levels (>0.92) in mucosa also showed significantly higher total folate concentrations (P=0.03) and gene expression levels of RFC-1 (P<0.01), GGH (P<0.01), and TS (P=0.04) compared with patients with low FPGS levels. The total reduced folate concentration correlated with the gene expression levels of RFC-1 and FPGS but not with TS or GGH. CONCLUSION: Our results suggest that normal-appearing colonic mucosa adjacent to primary colon cancer can show altered gene expression levels of FPGS that may have bearing on the development of aggressive metastatic behavior of the tumor and on tumor-specific survival.
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| 15. |
- 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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| 16. |
- Papadogiannakis, Nikos, et al.
(författare)
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Modes of adherence of Helicobacter pylori to gastric surface epithelium in gastroduodenal disease: A possible sequence of events leading to internalisation
- 2000
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Ingår i: APMIS : acta pathologica, microbiologica, et immunologica Scandinavica. - : Wiley. - 1600-0463 .- 0903-4641. ; 108:6, s. 439-447
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Tidskriftsartikel (refereegranskat)abstract
- We have investigated various modes of adherence of Helicobacter pylori to the human gastric epithelium, using transmission electron microscopy, in biopsies from nine patients with peptic ulcer disease and from four patients with chronic active gastritis. H. pylori was demonstrated in abundance in all cases within the surface mucous layer. In all ulcer- and in one out of four gastritis patients H. pylori was shown in close proximity to the gastric epithelium, with concurrent alterations in the configuration of microvilli and the apical cytoplasmic region of gastric cells. Previously described modes of H. pylori adherence were confirmed, such as loose attachment with fibrillar-like strands, firm attachment with pedestal formation, invasion in the intercellular spaces, and invagination with cup formation. Moreover, in many cases a fusion between the bacterial outer layer and gastric cell membranes was evident. In four cases (31; three with active and one with past ulcer disease) viable H. pylori was found in the cytoplasm of gastric mucous cells. Our results support the hypothesis that the different modes of adherence of H. pylori represent a stepwise, possibly sequential, process which in a significant number of cases leads to internalisation of the organism. The invariable occurrence of adhesion and more frequent internalisation of H. pylori in ulcer patients may suggest a link with the pathogenesis of peptic ulcer disease.
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| 17. |
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| 18. |
- Sjunnesson, Håkan, et al.
(författare)
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Comparative study of Helicobacter pylori infection in guinea pigs and mice - elevation of acute-phase protein C3 in infected guinea pigs
- 2001
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Ingår i: Pathogens and Disease. - 2049-632X. ; 30:2, s. 167-172
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Tidskriftsartikel (refereegranskat)abstract
- Eighteen Dunkin-Hartley guinea pigs and 50 NMRI mice were inoculated with Helicobacter pylori and the infection followed by culture, histopathology, antibody response, and plasma levels of the acute-phase proteins albumin, C3, and transferrin for up to 7 weeks. The immune response to H. pylori surface proteins was studied by an enzyme immunoassay (EIA) and Western immunoblot and the plasma levels of albumin, C3, and transferrin were analyzed by single radial immunodiffusion. Guinea pigs had a more severe gastritis and a higher EIA immune response than NMRI mice. Serum C3 levels were elevated in infected guinea pigs after 3 and 7 weeks indicating a systemic inflammatory response and a possible link between H. pylori infection and extragastric manifestations such as vasculitis associated with atherosclerosis. Serum cholesterol levels were analyzed in guinea pigs at 7 weeks and indicated a higher level in H. pylori-infected than in control animals, but this difference was not statistically significant.
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| 19. |
- 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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| 20. |
- Wang, Xin, et al.
(författare)
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Astaxanthin-rich algal meal and vitamin C inhibit Helicobacter pylori infection in BALB/cA mice
- 2000
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Ingår i: Antimicrobial Agents and Chemotherapy. - 1098-6596. ; 44:9, s. 2452-2457
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Tidskriftsartikel (refereegranskat)abstract
- Helicobacter pylori infection in humans is associated with chronic type B gastritis, peptic ulcer disease, and gastric carcinoma. A high intake of carotenoids and vitamin C has been proposed to prevent development of gastric malignancies. The aim of this study was to explore if the microalga Haematococcus pluvialis rich in the carotenoid astaxanthin and vitamin C can inhibit experimental H. pylori infection in a BALB/cA mouse model. Six-week-old BALB/cA mice were infected with the mouse-passaged H. pylori strain 119/95. At 2 weeks postinoculation mice were treated orally once daily for 10 days (i) with different doses of algal meal rich in astaxanthin (0.4, 2, and 4 g/kg of body weight, with the astaxanthin content at 10, 50, and 100 mg/kg, respectively), (ii) with a control meal (algal meal without astaxanthin, 4 g/kg), or (iii) with vitamin C (400 mg/kg). Five mice from each group were sacrificed 1 day after the cessation of treatment, and the other five animals were sacrificed 10 days after the cessation of treatment. Culture of H. pylori and determination of the inflammation score of the gastric mucosae were used to determine the outcome of the treatment. Mice treated with astaxanthin-rich algal meal or vitamin C showed significantly lower colonization levels and lower inflammation scores than those of untreated or control-meal-treated animals at 1 day and 10 days after the cessation of treatment. Lipid peroxidation was significantly decreased in mice treated with the astaxanthin-rich algal meal and vitamin C compared with that of animals not treated or treated with the control meal. Both astaxanthin-rich algal meal and vitamin C showed an inhibitory effect on H. pylori growth in vitro. In conclusion, antioxidants may be a new strategy for treating H. pylori infection in humans.
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