IgG3 and IgG4 Cells Are Increased in Active Ulcerative Colitis
Cells containing various subclasses of IgG and IgA were counted in the rectal and colonic mucosae from 14 pediatric patients with ulcerative colitis (UC) and in rectal biopsy specimens from 10 control subjects using monoclonal antibodies and the peroxidase-staining method. In both the patients and controls, the IgG1 cells predominated. The numbers of IgG1, IgG2, IgG3 and IgG4 cells were highest in the colonic specimens of patients with UC. The numbers of IgG3- and IgG4-containing cells were increased in the rectal mucosa of untreated UC patients compared to controls. In the rectal mucosa of patients with UC, the percentage of IgG2 cells was decreased compared to the controls (20 vs. 28%; p less than 0.05). In the great majority (37 out of 40) of specimens the number of IgA1 cells was higher than that of IgA2. The median number of IgA1 cells in the rectal specimens of untreated patients was slightly higher than that in the rectal specimens of the controls, for IgA2 the numbers were similar. Accentuation of colorectal IgG3 and IgG4 responses may be characteristic early changes in UC.
- [Show abstract] [Hide abstract] ABSTRACT: With the availability of increasingly potent acid-suppressing medications, questions continue to rise concerning the safety of these compounds in regards to carcinogenetic potential. In this review, we examine current concepts and procedures relating to genotoxicity, the potential for a chemical agent to interact with and alter the genomic information of the cell, and carcinogenesis. A description and discussion of commonly utilized techniques for the determination of (a) in vitro mutagenicity, (b) in vitro and in vivo DNA damage and repair, (c) in vitro and in vivo chromosomal damage and (d) chronically dosed animal tumorigenesis development is presented. Observations from these procedures as they have been applied to a review of the safety of acid-suppressing medications will be discussed. An evaluation of reports relating to potential genotoxic and carcinogenic hazards of therapeutically relevant acid-suppressing medications (cimetidine, ranitidine, omeprazole) is presented. Information related to the effect of prolonged administration of acid-suppressing medications, alterations of serum gastrin levels, and the potential for tumor promotion is discussed.0Comments 14Citations
- [Show abstract] [Hide abstract] ABSTRACT: The direct effects of omeprazole on colonic cells has not been evaluated. Controversy exists regarding the potential adverse effects of omeprazole on cell proliferation. In order to mimic the in vivo situation in the patient treated with omeprazole, proliferation cell culture experiments were performed, monitoring directly the effects of gastrin and omeprazole both alone and in combination. Three colonic cancer cell lines were used, two with neuroendocrine features (NCI-H716, LCC-18) and one (DLD-1) not known to have these features. In these in vitro proliferation experiments, only the NCI-H716 colorectal cancer cell line responded to omeprazole by decreased proliferation (P < 0.05). The effect was concentration dependent shown for all doses of omeprazole used. Gastrin had a statistically significant effect on increasing proliferation in the NCS-H716 cell line alone but only at the highest concentration (10(-6) M). Omeprazole has a cytostatic effect on one of three colorectal cancer cell lines but the mechanism for this effect of omeprazole and its potential role in treatment awaits elucidation.0Comments 8Citations
- [Show abstract] [Hide abstract] ABSTRACT: Histiocytic ulcerative colitis (HUC) is an inflammatory bowel disease (IBD) that occurs predominantly in dogs of the boxer breed. The lesions are characterized by mucosal ulceration and mixed inflammatory cell infiltrate that includes the presence of periodic acid-Schiff (PAS)-positive macrophages. However, the phenotype of the inflammatory cells has not been characterized further. In the present study, immunohistochemistry and computer-aided morphometric analysis were used to define populations of leucocyte subsets in the colon of 14 boxer dogs with HUC. Biopsies from six of these dogs included both lesional and non-lesional regions. Colonic tissue from 11 dogs of various breeds without evidence of gastrointestinal disease served as controls. In HUC lesions there were significantly more IgG(+), IgG3(+), IgG4(+)plasma cells, CD3(+)T cells, MHC class II(+)cells, L1(+)cells and PAS(+)cells in the lamina propria than in both control colon and non-lesional colonic regions of affected dogs. In the epithelial compartment, goblet cells were significantly decreased in HUC lesions compared to both control and non-lesional HUC colon, and intensity of enterocyte MHC class II expression was significantly increased. These observations are similar to those documented in human IBD, especially ulcerative colitis, and suggest an important role for the mucosal immune system in the pathogenesis of canine HUC.0Comments 43Citations