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  • 1
    ISSN: 1432-1203
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Fifteen apparently unrelated Dutch families with familial adenomatous polyposis (FAP) also known as familial polyposis coli (FPC; McKusick No. 17510) were screened for linkage with the DNA probe C11p11 localized on chromosome 5q21–22 and previously reported to be closely linked to FAP (Bodmer et al. 1987; Leppert et al. 1987). In our study C11p11 was minimally informative, which is ascribable to its low heterozygosity in the North European populations. Of the above families, 12 were investigated also for linkage with D5S37 (DNA probe Pi227). Data from 11 of them were found to be informative and showed that FAP is closely linked to D5S37 previously localized on chromosome 5q21 (peak lod score 7.85 at a recombination fraction of 0.048 with 95% probability limits 0.005–0.145). Results discussed below indicate for the first time that the most likely location of the FAP gene is in the band 5q22 very close to 5q21, if not in the transitional zone between these two bands. The probe Pi227 recognizes 4 restriction fragment length polymorphism (RFLP) sites, exhibiting a total of 9 alleles with 24 theoretically possible haplotypes in the Dutch population. Therefore, this probe appears to have potential as a generally useful predictive marker for FAP until much closer and similarly useful markers become available.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-1203
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Two independent study-groups, one in Britain and the other in the United States, were the first to report linkage between APC and a TaqI restriction fragment length polymorphism (RFLP) at D5S71 (probe C11p11) on chromosome 5q. They found no recombinants in about 50 informative meioses. The same TaqI RFLP was found to be uninformative for linkage in 15 Dutch polyposis families. The recently reported four base-pair deletion polymorphism (DEL1) at D5S71 has raised the polymorphism information content of this marker from 0.17 to 0.40 in the Dutch population. Seven of 20 polyposis families screened for the DEL1 as well as the TaqI polymorphism gave a combined peak lod score of 5.68 with no recombinants in 37 informative meioses. These data, together with those so far reported in the literature, raise the peak lod score to 17.09 at a recombination fraction of 0.05, the 95% upper confidence limit being 0.09. In combination with the use of another informative marker, D5S81 (probe YN5.48) closely mapping on the other side of APC, the presymptomatic diagnosis of the disease can be made with more than 99.9% certainty. It has to be stressed, however, that the the possible existence of more than one polyposis locus cannot, as yet, be excluded.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Amsterdam : Elsevier
    Free Radical Biology and Medicine 9 (1990), S. 501-506 
    ISSN: 0891-5849
    Keywords: Adenocarcinoma ; Adenomatous polyps ; Colon ; Free radicals ; Metallothionein ; Superoxide dismutase
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 0888-7543
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Biology , Medicine
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1365-2559
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: The histological, mucin histochemical and immunohistochemical features were evaluated of 74 solitary and 73 synchronous colorectal adenomas which were endoscopically removed from 124 patients. Of the patients, 60% had a single adenoma, whereas 40% had at least two adenomas in their colorectum. Comparing the incidence of synchronous adenomas in both sexes revealed a statistically significant higher incidence (P 〈 0.005) in males. The localization of the solitary and syn hronous adenomas in the large bowel was similar. Moreover, parameters of malignant change within the adenomas (size, predominant type of mucosal growth and degree of dysplasia—with the exception of severe dysplasia) as well as signs of dedifferentiation (relative proportions of goblet and columnar cells) were also similar. Mucin staining intensities (periodic acid-Schiff, high iron diamine and alcian blue) and the immunoreactivity patterns of secretory component and carcinoembryonic antigen, both cytoplasmic and on the surface of the epithelial cells, were also identical in both groups of adenomas. Thus, neither the routine histological nor the mucin-and immunohistochemical features differed between the groups, except for severe dysplasia. It is concluded that there is no inherent difference in malignant potential between solitary and synchronous adenomas, with the possible exception of the degree of dysplasia.
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1365-2559
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Carcinogenesis in the human colon is associated with a marked increase in the tissue content of the urokinase-type plasmmogen activator (u-PA). This study was performed to determine the type of cells responsible for the u-PA increase in carcinomas of the colon and in their precursor lesions, the adenomas, by immunohistological evaluation applying monoclonal antibody 3689 directed to the β-chain of u-PA.Normal intestinal mucosa (n= 17) showed hardly any staining of u-PA, but some lamina propria cells were faintly positive. Carcinomas (n= 17) and adenomas (n= 16) showed a considerable and comparable staining intensity of u-PA in neoplastic columnar epithelial cells, and this staining was found to be diffuse and cytoplasmic. In a majority of the neoplastic tissues the u-PA staining was found to be patchy and not related to known risk markers of malignancy such as dysplasia in the adenomas, or to prognostic determinants such as Dukes' classification or differentiation in the carcinomas. The observation of strong u-PA positive lamina propria cells in adenomas but infrequently observed in normal mucosa and carcinomas was noteworthy. u-PA staining intensity of the tissue sections was found to correlate well with the u-PA antigen level in the tissue extracts determined by ELISA (r= 0.52, P= 0.0001) but poorly with the u-PA activity determined enzymatically (r= 0.28, P= 0.05).In conclusion, the u-PA increase in neoplasia of the human colon can be attributed to an increased diffuse cytoplasmic content of u-PA in neoplastic columnar epithelial cells.
    Type of Medium: Electronic Resource
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  • 7
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Histopathology 25 (1994), S. 0 
    ISSN: 1365-2559
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: The expression of tetranectin in colonic neoplasia was evaluated by determining the tissue distribution by immunohistological analysis of tissue sections and the antigen levels in tissue homogenates and plasma. In normal colonic mucosa tetranectin staining was predominantly found in the goblet cells whereas in adenocarcinomas this staining was confined to the tumour stroma. Colonic adenomas, benign precursors of adenocarcinomas, showed fewer tetranectin positive goblet cells and in some cases showed tetranectin expression in the stroma. Within the tissue homogenates no differences were found in the tetranectin levels between normal mucosa, adenomas and carcinomas. Patients with colonic cancer were found to have significantly decreased plasma tetranectin levels compared to healthy controls. Thus, colonic neoplasia is associated with a change in the tissue distribution of tetranectin, without an obvious change in the tissue level, and a low plasma tetranectin level.
    Type of Medium: Electronic Resource
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  • 8
    ISSN: 1365-2036
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: 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 Resource
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  • 9
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Alimentary pharmacology & therapeutics 9 (1995), S. 0 
    ISSN: 1365-2036
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: 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 Resource
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  • 10
    ISSN: 1365-2036
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: 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 Resource
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