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Träfflista för sökning "WFRF:(Willén Roger) ;lar1:(gu)"

Sökning: WFRF:(Willén Roger) > Göteborgs universitet

  • Resultat 1-10 av 13
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1.
  • Bjursten, Malin, 1976, et al. (författare)
  • Long-term treatment with anti-alpha 4 integrin antibodies aggravates colitis in G alpha i2-deficient mice.
  • 2005
  • Ingår i: European journal of immunology. - : Wiley. - 0014-2980 .- 1521-4141. ; 35:8, s. 2274-83
  • Tidskriftsartikel (refereegranskat)abstract
    • Targeted deletion of the heterotrimeric G protein, Galphai2, in mice induces lethal colitis closely resembling ulcerative colitis. In chronic colitis, migration of circulating leukocytes into the intestinal mucosa is partially dependent on alpha4 integrins. In previous studies, short-term administration of anti-alpha4 integrin antibodies has been shown to attenuate intestinal inflammation, and here we elucidate the effect of long-term administration of anti-alpha4 integrin antibodies on colitis in Galphai2(-/- )mice. Long-term blockade of alpha4 integrin significantly increased the severity of colitis in Galphai2(-/-) mice. The inflammation was confined to the colon, associated with increased cancer in situ, destruction of crypt architecture, and increased production of IL-1beta, TNF-alpha and IFN-gamma. Blockade of alpha4 integrin reduced the recruitment of activated T cells to the small intestine. In strong contrast, there were significantly higher numbers of activated T cells in the colonic lamina propria and epithelium, most probably due to in situ proliferation. Furthermore, treatment with alpha4 integrin antibodies induced decreased levels of total IgA and IgG in sera, whereas total IgM levels were unchanged. These new findings may have implications in the understanding of the progression of chronic intestinal inflammation.
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2.
  • Bjursten, Malin, 1976, et al. (författare)
  • Transfer of colitis by Galphai2-deficient T lymphocytes: impact of subpopulations and tissue origin.
  • 2005
  • Ingår i: Inflammatory bowel diseases. - 1078-0998. ; 11:11, s. 997-1005
  • Tidskriftsartikel (refereegranskat)abstract
    • To elucidate the potential cell population(s) involved in the induction of colitis in inhibitory G protein Galphai2(-/-) mice, Galphai2-deficient or competent bone marrow or splenic and mesenteric lymph node (MLN) T cells were transferred into immunodeficient mice. The mice were followed up to 23 weeks after transfer, recording changes in body weight. Colitis was graded on hematoxylin and eosin-stained colonic tissue, and production of serum interleukin-18 and colon-derived interferon-gamma was measured using ELISA. After adoptive transfer of Galphai2(-/-) bone marrow, severe colitis developed in irradiated wild type recipients, whereas irradiated Galphai2(-/-) mice increased their life span more than 3 times after transfer of wild type bone marrow, accompanied by significant amelioration of colitis. Neither purified Galphai2(-/-) CD4(+), nor CD8(+) splenic or MLN-derived T cells could induce colitis in recombination-activating gene V(RAG) 2(-/-) recipient mice, whereas transfer of splenic Galphai2(-/-) CD3(+) T cells induced severe colitis. In contrast, transfer of Galphai2(-/-) CD3(+) T cells from the MLN caused only minor histopathological changes in the intestinal mucosa. Finally, serum levels of interleukin-18 and interferon-gamma production from colonic tissue cultures correlated well with disease severity. Our results show that bone marrow transplantation can prolong the life of Galphai2(-/-) mice and ameliorate intestinal inflammation. Splenic CD4(+) or CD8(+) T cells on their own were poor inducers of colitis, whereas the combination of both was highly involved in the induction of intestinal inflammation. Furthermore, we show that the tissue origin of CD3(+) T cells is critical for their potency to induce colitis.
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3.
  • Block, Mattias, 1968, et al. (författare)
  • Neoplasia in the colorectal specimens of patients with ulcerative colitis and ileal pouch-anal anastomosis - need for routine surveillance?
  • 2015
  • Ingår i: Scandinavian journal of gastroenterology. - : Informa UK Limited. - 1502-7708 .- 0036-5521. ; 50:5, s. 528-35
  • Tidskriftsartikel (refereegranskat)abstract
    • Patients who undergo ileal pouch-anal anastomosis (IPAA) after colectomy for ulcerative colitis (UC) occasionally have neoplasia in the IPAA. Patients with evidence of dysplasia or carcinoma in the colorectal specimen may have an increased risk of such neoplasia. A surveillance program has been suggested. The aims of this study were to evaluate the outcomes of surveillance of a large patient cohort, and to investigate the prevalences of neoplasia in the ileal pouch mucosa and in the anal transitional zone (ATZ).
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4.
  • Dahlgren, Eva, et al. (författare)
  • Sertoli-Leydig cell tumour in a postmenopausal woman showing all facets of the insulin resistance syndrome (IRS)
  • 2005
  • Ingår i: Ups J Med Sci. - 0300-9734. ; 110:3, s. 233-6
  • Tidskriftsartikel (refereegranskat)abstract
    • Sertoli-Leydig cell tumours are rare sex stromal tumours with an incidence of < 0.5% of all ovarian tumours. Most frequently this tumour occurs in young women with a history of amenorrhoea, hirsutism and lowered pitch. Here, we report on a woman with IRS, postmenopausal virilization and increased testosterone levels due to a Sertoli-Leydig cell tumour. This is the first case to suggest an association between IRS and Sertoli-Leydig cell tumours. Furthermore, we highlight the difficulties in detecting this ovarian tumour with sonography.
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5.
  • Elgbratt, Kristina, 1969, et al. (författare)
  • Aberrant T-cell ontogeny and defective thymocyte and colonic T-cell chemotactic migration in colitis-prone Galphai2-deficient mice
  • 2007
  • Ingår i: Immunology. - : Wiley. - 0019-2805 .- 1365-2567. ; 122:2, s. 199-209
  • 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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6.
  • Fredin, Maria Fritsch, 1970, et al. (författare)
  • The application and relevance of ex vivo culture systems for assessment of IBD treatment in murine models of colitis
  • 2008
  • Ingår i: Pharmacological Research. - : Elsevier BV. - 1043-6618 .- 1096-1186. ; 58:3-4, s. 222-231
  • Tidskriftsartikel (refereegranskat)abstract
    • The aim of this study was to investigate the relevance of mouse ex vivo cultures as a first screening model for new therapeutic agents of Inflammatory Bowel Disease (IBD). Two murine models (dextran sodium sulphate (DSS)-induced colitis and Gαi2-deficient mice) and two anti-inflammatory agents (methyl-prednisolone and the proteasome inhibitor MG132) were evaluated. The in vivo effects of methyl-prednisolone were assessed in both models. Ex vivo colonic tissue from both mouse models were cultured in the presence or absence of the drugs and TaqMan Low-Density arrays were used to assess the regulation of inflammatory genes before and after drug treatment. Colitis induced a similar inflammatory gene profile in both mouse models in in vivo studies and in ex vivo cultures. The differences encountered reflected the different phases of colitis in the models, e.g. innate cytokine/chemokine profile in the DSS model and T cell related markers in Gαi2-deficient mice. After steroid treatment, a similar pattern of genes was suppressed in the two mouse models. We confirmed the suppression of inflammatory gene expression for IL-1β, IL-6 and iNOS in ex vivo and in vivo colons from both mouse models by quantitative RT-PCR. Importantly, the inflammatory responses in the murine ex vivo culture system reflected the in vivo response in the inflamed colonic tissue as assessed by changes in inflammatory gene expression, suggesting that the murine culture system can be used for validation of future IBD therapies.
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7.
  • Odin, Elisabeth, 1955, et al. (författare)
  • Altered gene expression of folate enzymes in adjacent mucosa is associated with outcome of colorectal cancer patients.
  • 2003
  • 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
  • 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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8.
  • Odin, Elisabeth, 1955, et al. (författare)
  • Expression and clinical significance of methylenetetrahydrofolate reductase in patients with colorectal cancer
  • 2006
  • Ingår i: Clin Colorectal Cancer. - 1533-0028. ; 5:5, s. 344-9
  • 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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9.
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10.
  • Solberg, Anna, 1961, et al. (författare)
  • Progress of tissue injury in appendicitis involves the serine proteases uPA and PAI-1.
  • 2009
  • Ingår i: Scandinavian journal of gastroenterology. - : Informa UK Limited. - 1502-7708 .- 0036-5521. ; 44:5, s. 579-84
  • 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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