The effect of Helicobacter mustelae infection on gastric epithelial proliferation was studied in ferrets colonized with H.mustelae and specific pathogen-free (SPF) ferrets not infected with H.mustelae. Thirteen H. mustelae-infected ferrets between the ages of 13 and 32 months and 16 SPF ferrets between 6 and 18 months were analyzed. Bacterial cultures, urease tests and Warthin-Starry stains were used to identify H.mustelae. Tissues obtained from the antrum and the body regions of the stomach were assayed by proliferating cell nuclear antigen (PCNA) immunohistochemistry and measured using a computerized color image analysis system. PCNA-expressing gastric epithelia in the antrum and the body regions were significantly increased in the H.mustelae-infected ferrets versus the SPF ferrets (P < 0.001). PCNA positivity in the antrum regions of both the H.mustelae-infected ferrets and SPF ferrets was significantly higher than that of the body regions (P < 0.001). Comparison of the histopathology of infected ferrets indicated that PCNA positivity correlated with the histological severity of gastritis. This study suggests that cell proliferation in ferret gastric mucosa increases with H.mustelae infection and provides evidence that PCNA is a useful biomarker for studying the changes in cell kinetics in the ferret stomach. The data also further support the use of the H.mustelae-infected ferret as an animal model for studying the pathogenesis of Helicobacter pylori-induced gastric diseases of humans.
These results suggest that though prior infection with H. mustelae may confer some protection against reinfection, such protection is not universal in all circumstances; that susceptibility to reinfection by contact with infected animals varies between individuals; and that age may be a factor in this individual variability. These results are applicable to studies of reinfection after eradication of H. pylori in humans.
Oral vaccination of young ferrets with Hml and 50 micrograms MDP increased the risk of Helicobacter-associated mucosal ulceration in the proximal duodenum, which was associated with low humoral (but significant cell-mediated) immune responses to H. mustelae. In retrospect, the frequency of vaccination may have suppressed the systemic humoral immune response, thereby promoting mucosal damage by H. mustelae. The 50-microgram dose of MDP enhanced the cell-mediated immune response, which indirectly contributed to development of severe lesions. The increased frequency of mucosal damage associated with this vaccination regimen enhances the value of the ferret model for studying duodenal ulceration secondary to Helicobacter infection.
Abstract. Eosinophilic gastroenteritis, focal or diffuse with eosinophilic infiltrations of the stomach or intestine, has been described in human beings, cats, dogs, and horses. In this paper, we describe infiltration of the gastrointestinal tract with eosinophils accompanied by a circulating eosinophilia in six ferrets (Mustela putorius furoi. Clinical signs included chronic weight loss, anorexia, and diarrhea. The small intestines from five ferrets had diffuse infiltrates of eosinophils. This resulted in focal or multifocal loss of the muscular tunic in three ferrets. Two of these ferrets also had eosinophilic gastritis. Eosinophilic granulomas with SplendoreHoeppli material were present in mesenteric lymph nodes in four ferrets. Two ferrets had multiple organ involvement; one had eosinophilic granulomas in the liver, mesentery, and choroid plexus as well as moderate parapancreatic segmental arteritis with infiltration of eosinophils and mural thrombosis. The second ferret had, in addition to moderate diffuse gastric and small intestinal eosinophilic mucosal infiltrations, interstitial eosinophilic pulmonary infiltrates. Examination of all tissues failed to reveal an infectious agent.
By using a murine monoclonal antibody produced against an IL 2-dependent human T cell line, we defined a T lineage-specific molecule, termed Ta1, that is expressed strongly on activated T lymphocytes of both the T4 and T8 subsets, as well as on T cell lines and clones, but only weakly on a fraction of resting T cells. SDS-PAGE analysis of immunoprecipitates from 125I-labeled, activated T cells demonstrates a single major band of apparent m.w. 105 KD under both reducing and nonreducing conditions. Unlike anti-IL 2 receptor antibodies, anti-Ta1 does not inhibit T cell proliferative responses to mitogen, antigen, or IL 2-containing medium. Moreover, anti-Ta1 has no effect on T cell-mediated cytotoxicity. Ta1 appears to be a novel human T cell-specific activation antigen that may serve as a useful marker of T cell activation in human disease.
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