Search Results - (Author, Cooperation:H. W. Verspaget)
-
1Latest Papers from Table of Contents or Articles in PressL. Jostins ; S. Ripke ; R. K. Weersma ; R. H. Duerr ; D. P. McGovern ; K. Y. Hui ; J. C. Lee ; L. P. Schumm ; Y. Sharma ; C. A. Anderson ; J. Essers ; M. Mitrovic ; K. Ning ; I. Cleynen ; E. Theatre ; S. L. Spain ; S. Raychaudhuri ; P. Goyette ; Z. Wei ; C. Abraham ; J. P. Achkar ; T. Ahmad ; L. Amininejad ; A. N. Ananthakrishnan ; V. Andersen ; J. M. Andrews ; L. Baidoo ; T. Balschun ; P. A. Bampton ; A. Bitton ; G. Boucher ; S. Brand ; C. Buning ; A. Cohain ; S. Cichon ; M. D'Amato ; D. De Jong ; K. L. Devaney ; M. Dubinsky ; C. Edwards ; D. Ellinghaus ; L. R. Ferguson ; D. Franchimont ; K. Fransen ; R. Gearry ; M. Georges ; C. Gieger ; J. Glas ; T. Haritunians ; A. Hart ; C. Hawkey ; M. Hedl ; X. Hu ; T. H. Karlsen ; L. Kupcinskas ; S. Kugathasan ; A. Latiano ; D. Laukens ; I. C. Lawrance ; C. W. Lees ; E. Louis ; G. Mahy ; J. Mansfield ; A. R. Morgan ; C. Mowat ; W. Newman ; O. Palmieri ; C. Y. Ponsioen ; U. Potocnik ; N. J. Prescott ; M. Regueiro ; J. I. Rotter ; R. K. Russell ; J. D. Sanderson ; M. Sans ; J. Satsangi ; S. Schreiber ; L. A. Simms ; J. Sventoraityte ; S. R. Targan ; K. D. Taylor ; M. Tremelling ; H. W. Verspaget ; M. De Vos ; C. Wijmenga ; D. C. Wilson ; J. Winkelmann ; R. J. Xavier ; S. Zeissig ; B. Zhang ; C. K. Zhang ; H. Zhao ; M. S. Silverberg ; V. Annese ; H. Hakonarson ; S. R. Brant ; G. Radford-Smith ; C. G. Mathew ; J. D. Rioux ; E. E. Schadt ; M. J. Daly ; A. Franke ; M. Parkes ; S. Vermeire ; J. C. Barrett ; J. H. Cho
Nature Publishing Group (NPG)
Published 2012Staff ViewPublication Date: 2012-11-07Publisher: Nature Publishing Group (NPG)Print ISSN: 0028-0836Electronic ISSN: 1476-4687Topics: BiologyChemistry and PharmacologyMedicineNatural Sciences in GeneralPhysicsKeywords: Colitis, Ulcerative/genetics/immunology/microbiology/physiopathology ; Crohn Disease/genetics/immunology/microbiology/physiopathology ; Genetic Predisposition to Disease/*genetics ; Genome, Human/genetics ; *Genome-Wide Association Study ; Haplotypes/genetics ; *Host-Pathogen Interactions/genetics/immunology ; Humans ; Inflammatory Bowel Diseases/*genetics/immunology/*microbiology/physiopathology ; Mycobacterium/*immunology/pathogenicity ; Mycobacterium Infections/genetics/microbiology ; Mycobacterium tuberculosis/immunology/pathogenicity ; Phenotype ; Polymorphism, Single Nucleotide/genetics ; Reproducibility of ResultsPublished by: -
2Articles: DFG German National LicensesVAN DE WAL, Y. ; VEER, A. VAN DER SLUYS ; VERSPAGET, H. W. ; MULDER, T. P. J. ; GRIFFIOEN, G. ; VAN TOL, E. A. F. ; PEÑA, A. S. ; LAMERS, C. B. H. W.
Oxford, UK : Blackwell Publishing Ltd
Published 1993Staff ViewISSN: 1365-2036Source: Blackwell Publishing Journal Backfiles 1879-2005Topics: MedicineNotes: Disturbances in zinc metabolism have been documented in patients with inflammatory bowel disease. In this study we evaluated the effect of in vivo treatment with zinc on the in vitro natural killer cell activity in thirteen inflammatory bowel disease patients, with stable disease and mild–moderate disease activity, in a double-blind randomized cross-over trial. The results of our study show a long-lasting effect of in vivo zinc administration, which decreased peripheral blood natural killer cell activity in inflammatory bowel disease.Type of Medium: Electronic ResourceURL: -
3Articles: DFG German National LicensesVAN IERSSEL, A. J. H. M. ; MIEREMET-OOMS, M. A. C. ; VAN DER ZON, J. M. ; VAN HOGEZAND, R. A. ; GRIFFIOEN, G. ; LAMERS, C. B. H. W. ; VERSPAGET, H. W.
Oxford BSL : Blackwell Science
Published 1997Staff ViewISSN: 1365-2036Source: Blackwell Publishing Journal Backfiles 1879-2005Topics: MedicineNotes: Background: Corticosteroid therapy of patients with inflammatory bowel disease can give rise to systemic side-effects. Budesonide is a topically acting corticosteroid with low systemic bioavailability and is efficacious in the treatment of inflammatory bowel disease. Natural killer cells were previously found to be altered, both systemically and locally, in patients with inflammatory bowel disease. Modulatory effects of budesonide, prednisolone, dexamethasone, and cortisol on peripheral blood NK cells have already been described, but have never been assessed on mucosal NK cells from the intestine. Methods: The effect of the synthetic corticosteroids prednisolone and budesonide, the endogenous corticosteroid cortisol, and adrenocorticotropic hormone was analysed on NK cells isolated from the lamina propria of human intestinal resection specimens. Results: The three corticosteroids suppressed intestinal NK cell activity, not only during the cytotoxicity assay, but also after pre-incubation of the lamina propria mononuclear cells. ACTH, however, did not affect the activity of intestinal NK cells. We previously showed that corticosteroid-suppressed peripheral blood NK cell activity could be restored in vivo, but not in vitro, by the administration of ACTH. In the present study, the in vitro incubation of budesonide- or prednisolone-suppressed mucosal NK cells with cortisol, alone or combined with ACTH, did not revert the suppressed NK cell activity. These findings are similar to our previous observations with peripheral blood NK cells. Conclusions: Intestinal mucosal NK cells can be suppressed by systemically as well as locally acting corticosteroids. This suppression in NK cell activity is not reversed by incubation with cortisol and/or ACTH.Type of Medium: Electronic ResourceURL: -
4Articles: DFG German National LicensesGao, Q. ; Hogezand, R. A. ; Lamers, C. B. H. W. ; Verspaget, H. W.
Oxford, UK : Blackwell Science Ltd
Published 2004Staff ViewISSN: 1365-2036Source: Blackwell Publishing Journal Backfiles 1879-2005Topics: MedicineNotes: Background : Fibroblast growth factors play an important role in (patho)physiological processes such as wound healing and tissue repair. We previously showed that basic fibroblast growth factor is actively involved in inflammatory bowel disease processes. In the present retrospective study, we assessed whether serum basic fibroblast growth factor levels in Crohn's disease patients reflect the response to anti-tumour necrosis factor-α antibody infliximab treatment.Aim and methods : Serum samples, biopsies and patient data from a subgroup of patients included in two placebo-controlled trials were used. Fistulizing Crohn's disease patients (n = 42) were administered placebo or infliximab intravenously three times and evaluated for response up to 18 weeks. Biopsies from a subgroup of patients were stained for basic fibroblast growth factor using indirect immunohistochemistry. In the active Crohn's disease trial, patients (n = 24) received either placebo or infliximab once, and disease activity and serum basic fibroblast growth factor were assessed at weeks 0 and 4.Results : Basic fibroblast growth factor levels at inclusion were comparable in the fistulizing Crohn's disease patients regardless of whether the fistulas did or did not respond or completely heal (median range: 9.3–10.6 pg/mL). At the end of follow-up basic fibroblast growth factor levels were lower in patients who responded (9.2 pg/mL, P = 0.06) or who were completely healed (8.9 pg/mL, P = 0.009) when compared with patients did not respond/heal (14.5 pg/mL), the latter not significantly increased from baseline. Decreases in the perianal disease activity index and open fistula scores at the end of the follow-up were significantly correlated with the decrease in basic fibroblast growth factor (R = 0.41; P = 0.012 and R = 0.35; P =0.027, respectively). Immunohistological evaluation also showed a trend towards decreased basic fibroblast growth factor expression in intestinal biopsies of these patients. Patients with active disease, i.e. a Crohn's disease activity index ≥220 combined from the two studies, were found to have significantly (P = 0.0046) lower baseline serum basic fibroblast growth factors levels than those with inactive disease (5.3 vs. 10.3pg/mL, respectively). Treatment of the active disease patients did not affect the serum basic fibroblast growth factor level, although a general decrease in disease activity was observed with infliximab treatment.Conclusions : Healing of fistulizing/perianal Crohn's disease seems to be reflected by a decrease in high serum basic fibroblast growth factor. Basic fibroblast growth factor levels do not relate with response in active Crohn's disease patients.Type of Medium: Electronic ResourceURL: -
5Articles: DFG German National LicensesNIELSEN, O. H. ; VERSPAGET, H. W. ; ELMGREEN, J.
Oxford, UK : Blackwell Publishing Ltd
Published 1988Staff ViewISSN: 1365-2036Source: Blackwell Publishing Journal Backfiles 1879-2005Topics: MedicineNotes: Purified intestinal macrophages obtained at resections for colonic neoplasms were investigated for chemotaxis to leukotriene B4 (LTB4) by the Millipore filter assay and leading front technique. Possible inhibition by drugs effective in the treatment of chronic inflammatory bowel disease (sulphasalazine, olsalazine, its active moiety 5-aminosalicylic acid (5-ASA), and the 5-ASA metabolite N-acetylated-5-ASA (ac-5-ASA)) was tested at therapeutic colonic concentrations of 0.01–10 mm. Leukotriene B4 at a dose of 10 nm was equipotent with casein (5 g litre—1) as regards chemoattraction of macrophages. Sulphasalazine, olsalazine and 5-ASA were potent inhibitors of macrophages chemotaxis to LTB4 with IC50 values of 0.43, 0.39 and 0.24 mm, respectively. These concentrations are below the lowest concentration of 5—ASA (2 mm) in the colonic lumen during conventional sulphasalazine treatment of patients with chronic inflammatory bowel disease. The inhibition of macrophage chemotaxis by these drugs may be important for this limitation of the local inflammatory process in chronic inflammatory bowel disease, and may in part explain the beneficial effect of systemic and local treatment with sulphasalazine. Leukotriene B4 appears to be an important inflammatory mediator for the activation of macrophages in colonic inflammation.Type of Medium: Electronic ResourceURL: -
6Articles: DFG German National LicensesStaff View
ISSN: 1365-2036Source: Blackwell Publishing Journal Backfiles 1879-2005Topics: MedicineNotes: Virtually all inflammatory mediators investigated to date seem to be dysregulated in the inflamed intestinal mucosa of patients with inflammatory bowel disease. However, which of these are actually involved in the initiation and perpetuation of intestinal tissue damage is still not fully understood. Amongst these mediators are the reactive oxygen metabolites, produced in large amounts by the massively infiltrating leucocytes. These reactive oxygen metabolites are believed to constitute a major tissue-destructive force and may contribute significantly to the pathogenesis of inflammatory bowel disease.This paper provides a concise overview of reactive oxygen metabolite biochemistry, the types of cell and tissue damage potentially inflicted by them, and the endogenous antioxidants which should prevent these harmful effects. An up-to-date summary of the available human experimental data suggests that reactive oxygen metabolite-mediated injury is important in both the primary and downstream secondary pathophysiological mechanisms underlying intestinal inflammation. Nonetheless, how the individual components of the mucosal antioxidant enzymatic cascade respond to inflammatory conditions is a neglected area of research. This particular aspect of intestinal mucosal oxidative stress therefore merits further study, in order to provide a sound, scientific basis for the design of antioxidant-directed treatment strategies for inflammatory bowel disease patients.Type of Medium: Electronic ResourceURL: -
7Articles: DFG German National LicensesIERSSEL, A. J. H. M. ; SLUYS VEER, A. ; VERSPAGET, H. W. ; GRIFFIOEN, G. ; HOGEZAND, R. A. ; LAMERS, C. B. H. W.
Oxford, UK : Blackwell Publishing Ltd
Published 1995Staff ViewISSN: 1365-2036Source: Blackwell Publishing Journal Backfiles 1879-2005Topics: MedicineNotes: Aim: To study the effect of oral budesonide and prednisolone on peripheral blood natural killer (NK) cell activity in patients with active ileocaecal Crohn's disease (Crohn's disease activity index, CDAI ≧ 200). Methods: One group of patients was treated for 10 weeks with oral budesonide (n= 9; 9 mg/day), and another group of patients for the same period with prednisolone (n= 9; 40 mg/day). Budesonide was tapered to 6 mg/day after 8 weeks and prednisolone after 2 weeks to 5 mg/day in the last week. Before treatment, and at 2, 4 and 10 weeks of treatment, natural killer cell activity was determined with a 51Cr release assay, and the number of CD16+ NK cells by Fluoresence activated cell sorter (FACS) analysis. Results: Budesonide, as well as prednisolone treatment, significantly decreased natural killer cell activity at weeks 2 and 4. This decrease was found to be accompanied by a similar decrease in the number of CD16+ NK cells. At 10 weeks, natural killer cell activity had almost returned to pre-treatment levels in the budesonide group and was significantly higher than pre-treatment levels in the prednisolone group. Disease activity was significantly decreased in all patients at week 2 until the end of the trial period. Conclusion: Both budesonide and prednisolone treatment suppress peripheral blood natural killer cell activity of patients with active ileocaecal Crohn's disease by decreasing the numbers of CD16+ NK cells in the circulation.Type of Medium: Electronic ResourceURL: -
8Articles: DFG German National LicensesVerspaget, H. W. ; Van Der Zon, A. M. ; Gao, Q. ; Van Hogezand, R. A.
Oxford UK : Blackwell Science Ltd
Published 2001Staff ViewISSN: 1365-2036Source: Blackwell Publishing Journal Backfiles 1879-2005Topics: MedicineType of Medium: Electronic ResourceURL: -
9Articles: DFG German National LicensesStaff View
ISSN: 1420-9071Keywords: Metallothionein ; liver ; primary biliary cirrhosis ; copper ; zincSource: Springer Online Journal Archives 1860-2000Topics: BiologyMedicineNotes: Summary A copper-containing protein was purified from the liver of a patient with primary biliary cirrhosis by a combination of gel filtration and anion exchange chromatography. This copper-protein had UV absorption and emission spectra, an amino acid composition, and a molecular mass which were characteristic for metallothionein (MT). From 8 livers (3 control, 1 fetal and 4 primary biliary cirrhosis) MT was extracted with non-reducing buffer and centrifuged, and the pellets were re-extracted with a 1% 2-mercaptoethanol-containing buffer. The non-reducing buffer extracted a predominantly copper-containing MT from the livers of patients with primary biliary cirrhosis and a predominantly zinc-containing MT from control lives and the fetal liver. Only from the fetal liver was a copper/zinc containing MT solubilized during the re-extraction with 2-mercaptoethanol-containing buffer. These results indicate that human MT is a unique metalloprotein with age and disease-dependent characteristics.Type of Medium: Electronic ResourceURL: -
10Articles: DFG German National LicensesStaff View
ISSN: 1432-1335Keywords: Key words Ovarian cancer ; Metallothionein ; Response ; SurvivalSource: Springer Online Journal Archives 1860-2000Topics: MedicineNotes: Abstract Background and purpose: Regimens containing platinum drugs continue to be amongst the most effective therapies for ovarian cancer. However, despite high initial response rates most patients relapse and die of their disease. Elevation of metallothionein has been implicated as a mechanism by which tumour cells become resistant to platinum anticancer drugs, although most of these studies have been carried out in vitro. This study was carried out to determine whether metallothionein expression was associated with response or survival in patients with epithelial ovarian cancer. Methods: Metallothionein was determined by radioimmune assay using frozen ovarian tumour tissue taken either before or following cytotoxic chemotherapy. Results: An increase in expression of metallothionein was seen in tumour tissue from patients who had undergone cytotoxic chemotherapy, although this did not attain significance. However, a preliminary study using biopsy material from the same patient, taken both before and after chemotherapy, showed a statistically significant increase in metallothionein. An analysis of these data showed that the level of metallothionein expression was not associated with survival or response. Conclusion: These data do not support the hypothesis that metallothionein expression is a determinant of response in ovarian cancer. There is some preliminary evidence from the study of paired samples which indicates that cytotoxic chemotherapy may increase metallothionein expression. An increase in metallothionein was also seen in the study using unmatched biopsies although this did not attain statistical significance, due in part to the large inter-patient variability in expression of this protein.Type of Medium: Electronic ResourceURL: -
11Articles: DFG German National LicensesJanssen, A. M. L. ; Bosman, C. B. ; Kruidenier, L. ; Griffioen, G. ; Lamers, C. B. H. W. ; van Krieken, J. H. J. M. ; van de Velde, C. J. H. ; Verspaget, H. W.
Springer
Published 1999Staff ViewISSN: 1432-1335Keywords: Key words Adenomas ; Colorectal cancer ; Liver metastases ; Superoxide dismutasesSource: Springer Online Journal Archives 1860-2000Topics: MedicineNotes: Abstract Purpose : The oxidant-antioxidant balance within tissues is thought to contribute to the development and progression of cancer. Previous investigations have indicated changes in this balance during the colorectal oncogenic process that merit further investigation. The aim of the present study was to evaluate whether the human colorectal cancer sequence is accompanied by changes in the protein and activity levels of the antioxidant enzymes manganese- and copper/zinc-superoxide dismutase (Mn-SOD and Cu/Zn-SOD). Patients and methods : SOD levels were assessed in colorectal adenomas, carcinomas, and liver metastases and were compared with those in the corresponding normal tissues (n=35 in each group). Mn- and Cu/Zn-SOD expression was first evaluated semiquantitatively by electrophoretic activity analysis, immunoblotting, and immunohistochemistry and was subsequently quantified by enzyme-linked immunosorbent assays (ELISAs) and spectrophotometric activity assays. Results : The semiquantitative analyses showed enhanced Mn-SOD levels, primarily localized in (neoplastic) epithelial cells, in carcinomas, and in liver metastases as compared with adenomas and normal mucosa, whereas no consistent pattern was observed for Cu/Zn-SOD. Normal liver tissue expressed the highest levels of both SODs. The quantitative SOD analyses confirmed these observations and revealed that carcinomas and liver metastases expressed 2–4 times more Mn-SOD protein and enzymatic activity (0.0005 〈 P ≤ 0.01) than did the normal mucosa. Adenomas expressed intermediate Mn-SOD levels, which increased significantly with the diameter and tended to increase with the grade of dysplasia and presence of a villous component. In contrast, adenomas, carcinomas, and the corresponding normal mucosa were found to have a similar Cu/Zn-SOD content, whereas liver metastases contained significantly (P 〈 0.02) more Cu/Zn-SOD as compared with these tissues. In addition, the Cu/Zn-SOD content was not related to any histopathological characteristic of the carcinomas or adenomas. Conclusions : Our study indicates that the development of neoplasia in the human colorectum is accompanied by major changes in the level and activity of Mn-SOD. This observation illustrates that Mn-SOD might have a functional role in human colorectal carcinogenesis.Type of Medium: Electronic ResourceURL: -
12Articles: DFG German National LicensesArndt, J. W. ; Crama-Bohbouth, G. E. ; Verspaget, H. W. ; Blok, D. ; Pena, A. S. ; Tham, R. T. O. T. A. ; Weterman, I. T. ; Lamers, C. B. H. W. ; Pauwels, E. K. J.
Springer
Published 1989Staff ViewISSN: 1619-7089Keywords: 111In-granulocytes ; Image quality ; Inflammatory bowel disease ; LeukoscintigraphySource: Springer Online Journal Archives 1860-2000Topics: MedicineNotes: Abstract This study was undertaken to investigate the influence of various parameters of injected autologous 111In labelled granulocytes on scintigraphic image quality. Forty-two scintigrams of 37 patients with inflammatory bowel disease were evaluated. The images were divided into three groups according to quality: good, intermediate and poor. The relationships between image quality and such radiopharmaceutical parameters as injected dose of 111In, number of injected cells and specific activity were investigated. It appeared that in order to obtain interpretable images, a specific activity of at least 85 kBq 111In/million cells was necessary. The activity of the injected dose must exceed 7 MBq if poor quality images and very long acquisition times are to be avoided.Type of Medium: Electronic ResourceURL: