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Sökning: WFRF:(Willén Roger)

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  • [1]2345Nästa
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  • Agnarsdottir, Margret, et al. (författare)
  • Malacoplakia and spermatic granuloma complicating vasectomy
  • 2006
  • Ingår i: Uppsala Journal of Medical Sciences. - : Taylor & Francis. - 0300-9734 .- 2000-1967. ; 111:2, s. 227-230
  • Tidskriftsartikel (refereegranskat)abstract
    • Malacoplakia is a granulomatous disease with a histiocytic infiltrate containing calcified structures called Michaelis-Gutmann bodies. These structures are considered to represent an abnormal response to infection involving defective lysosomes and abnormal microbubular assembly. The disease most frequently involves urinary and genital tracts, but has also been described from most other organs. Here we present the first case of malacoplakia only involving the vas deferens.
  • Andreasson, Hakan, et al. (författare)
  • Histopathological Classification of Pseudomyxoma Peritonei and the Prognostic Importance of PINCH Protein
  • 2012
  • Ingår i: Anticancer Research. - : International Institute of Anticancer Research (IIAR). - 0250-7005 .- 1791-7530. ; 32:4, s. 1443-1448
  • Tidskriftsartikel (refereegranskat)abstract
    • Aim: The aims of this study were i) to assess a new and more detailed histopathological classification and to analyze concordance between pathologists in the histopathological classification of pseudomyxoma peritonei (PMP); ii) to analyze the expression in the stroma of the particularly interesting new cysteine-histidine (PINCH) protein and its prognostic importance in PMP. Materials and Methods: Surgical specimens from 81 patients, classified according to the Ronnett et al histopathological classification were compared to a new system with four groups ranging from indolent to aggressive growth patterns. PINCH protein expression was analyzed and was related to clinical variables. Results: The new four-group classification provided better prognostic information than the classification according to Ronnett et al. (p=0.04). Expression of the PINCH protein in the stroma was found in 83% of the cases and was associated with high tumor burden (p=0.002) and a poor prognosis (p=0.04). Conclusion: The proposed new PMP classification system may provide additional prognostic information. PINCH protein is expressed in PMP and has prognostic information.
  • 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. - 0014-2980. ; 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.
  • 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.
  • 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. - 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.
  • Holgersson, Georg, et al. (författare)
  • The prognostic value of pre-treatment thrombocytosis in two cohorts of patients with non-small cell lung cancer treated with curatively intended chemoradiotherapy
  • 2017
  • Ingår i: Neoplasma (Bratislava). - Bratislava : AEPress. - 0028-2685 .- 1338-4317. ; 64:6, s. 909-915
  • Tidskriftsartikel (refereegranskat)abstract
    • Chemoradiotherapy is the standard of care for inoperable stage III non-small cell lung cancer (NSCLC). This treatment, however, offers only a small chance of cure and is associated with many side effects. Little research has been made concerning which patients benefit most/least from the treatment. The present study evaluates the prognostic value of anemia, leukocytosis and thrombocytosis at diagnosis in this treatment setting. In the present study, data were collected retrospectively for 222 patients from two different phase II studies conducted between 2002-2007 in Sweden with patients treated with chemoradiotherapy for stage IIIA-IIIB NSCLC. Clinical data and the serum values of hemoglobin (Hgb), White blood cells (WBC) and Platelets (Plt) at enrollment were collected for all patients and studied in relation to overall survival using Kaplan-Meier product-limit estimates and a multivariate Cox proportional hazards regression model. The results showed that patients with thrombocytosis (Plt > 350 x 109 /L) had a shorter median overall survival (14.5 months) than patients with normal Plt at baseline (23.7 months). Patients with leukocytosis (WBC > 9 x 109 /L) had a shorter median survival (14.9 months) than patients with a normal WBC at baseline (22.5 months). However, in a multivariate model including all lab parameters and clinical factors, only thrombocytosis and performance status displayed a prognostic significance. In Conclusion, thrombocytosis showed to be an independent prognostic marker associated with shorter overall survival in stage III NSCLC treated with curatively intended chemoradiotherapy. This knowledge can potentially be used together with established prognostic factors, such as performance status when choosing the optimal therapy for the individual patient in this clinical setting
  • 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.
  • Bengtsson, Jonas, 1961, et al. (författare)
  • Can a failed ileal pouch anal anastomosis be left in situ?
  • 2007
  • Ingår i: Colorectal disease. - 1462-8910 .- 1463-1318. ; 9:6, s. 503-8
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE: Failure after ileal pouch-anal anastomosis (IPAA) is reported with a frequency of 10-20%. The failed IPAA can be excised or defunctioned. Indications for excision and further management of an indefinitely diverted pouch are poorly described. The aim of the present investigation was to investigate pouch-related problems and the histopathological pattern of the pouch mucosa in this group of patients. METHOD: In a cohort of 620 patients having IPAA with a median follow-up of 14 years, 56 patients with failure were identified. The patients with defunctioned pouches were assessed with regard to pouch-related problems and endoscopy with biopsies was performed. Biopsies were stained with haematoxylin-eosin, PAS for neutral mucins and Alcian blue/high iron diamine for sialomucins/sulphomucins. Morphological changes were grouped into three types modified according to Veress and assessed for dysplasia. RESULTS: Twenty-two patients with an indefinitely diverted pouch were found. The follow-up time after surgery for failure was 10 years. Thirteen patients completed the follow-up. Except for two patients with pelvic/perineal pain, there were no clinical problems. The majority of patients displayed mild to moderate macroscopic signs of inflammation. Morphologically, findings ranged from a preserved mucosal pattern to intense inflammatory reaction. No case of dysplasia or carcinoma was found. CONCLUSION: Most patients with an indefinitely diverted pouch had no complaints regarding the pouch. There was no case of dysplasia. Indefinite diversion may be preferable to pouch excision, especially given the associated morbidity.
  • 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. - : Taylor & Francis. - 0300-9734. ; 110:3, s. 233-236
  • 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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